Endre søk
Begrens søket
123 1 - 50 of 134
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Alkadarou, Tayseer
    et al.
    Musa, Ahmed
    Alkadarou, Abedelgader
    Mahfouz, Mohamed S
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Elhassan, Ahmed M
    Elhassan, Ibrahim M
    Immunological characteristics of hyperreactive malarial splenomegaly syndrome in sudanese patients2013Inngår i: Journal of Tropical Medicine, ISSN 1687-9686, E-ISSN 1687-9694, Vol. 2013, s. 961051-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hyperreactive Malarial Splenomegaly (HMS) is defined as a massive enlargement of the spleen resulting from abnormal immune responses after repeated exposure to the malaria parasites. This study was carried out in Khartoum, Sudan. Sudan is considered to be one of the countries where HMS is quite prevalent. The objective of the study was to determine the incidence of HMS in patients who reported to the Omdurman Tropical Diseases Hospital (OMTDH) in Sudan and to investigate the basic laboratory and immunological characteristics of this condition in these patients. A cross-sectional study was carried out in OMTDH, and all patients with enlarged spleens were included in the study. Thirty-one out of 335 (9.3%) patients were diagnosed as having the HMS condition using international criteria for HMS diagnosis. The mean serum immunoglobulin M (IgM) levels in HMS patient groups were 14.3 ± 5 g/L, and this was significantly higher compared with geographically matched controls (P < 0.001). Immunoglobulin G (IgG) C anticircumsporozoite (CSP) antibody levels were higher in the HMS patients although the difference was not statistically significant, when compared with a group of patients with mild malaria. In comparison with naïve European controls, both the HMS and the mild malaria groups had significantly higher antimalarial antibody levels P < 0.001 and P < 0.01, respectively. Plasma levels of interleukin 10 (IL10) and interferon gamma (IFN γ ) were significantly increased in the HMS patients compared with the healthy control donors (P < 0.05 and P < 0.01) for IL10 and IFN γ , respectively. The findings of this study suggest that HMS is one of the significant causes of tropical splenomegaly in Sudan. HMS is associated with significant elevations of circulating IgM and antimalarial IgG antibodies as well as IL10 and IFN γ .

  • 2. Amoako-Sakyi, Daniel
    et al.
    Adukpo, Selorme
    Kusi, Kwadwo A.
    Dodoo, Daniel
    Ofori, Michael F.
    Adjei, George O.
    Edoh, Dominic E.
    Asmah, Richard H.
    Brown, Charles
    Adu, Bright
    Obiri-Yeboah, Dorcas
    Futagbi, Godfred
    Abubakari, Sharif Buari
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Akanmori, Bartholomew D.
    Goka, Bamenla Q.
    Arko-Mensah, John
    Gyan, Ben A.
    A STAT6 Intronic Single-Nucleotide Polymorphism is Associated with Clinical Malaria in Ghanaian Children2016Inngår i: Genetics and Epigenetics, ISSN 1179-237X, Vol. 8, s. 7-14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Malaria pathogenesis may be influenced by IgE responses and cytokine cross-regulation. Several mutations in the IL-4/STAT6 signaling pathway can alter cytokine cross-regulation and IgE responses during a Plasmodium falciparum malarial infection. This study investigated the relationship between a STAT6 intronic single-nucleotide polymorphism (rs3024974), total IgE, cytokines, and malaria severity in 238 Ghanaian children aged between 0.5 and 13 years. Total IgE and cytokine levels were measured by ELISA, while genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Compared with healthy controls, heterozygosity protected against clinical malaria: uncomplicated malaria (odds ratios [OR] = 0.13, P < 0.001), severe malarial anemia (OR = 0.18, P, 0.001), and cerebral malaria (OR = 0.39, P = 0.022). Levels of total IgE significantly differed among malaria phenotypes (P = 0.044) and rs3024974 genotypes (P = 0.037). Neither cytokine levels nor IL-6/IL-10 ratios were associated with malaria phenotypes or rs3024974 genotypes. This study suggests a role for rs3024974 in malaria pathogenesis and offers further insights into an IL-4/STAT6 pathway mutation in malaria pathogenesis.

  • 3. Amodu, O. K.
    et al.
    Olaniyan, S. A.
    Adeyemo, A. A.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Olumese, P. E.
    Omotade, O. O.
    Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria2012Inngår i: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 123, nr 2, s. 72-77Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI95%: 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group 0 was demonstrated with a decreased risk of severe malaria OR=0.743 (CI95%: 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI95%: 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children.

  • 4. Anchang-Kimbi, Judith K.
    et al.
    Achidi, Eric A.
    Apinjoh, Tobias O.
    Mugri, Regina N.
    Chi, Hanesh Fru
    Tata, Rolland B.
    Nkegoum, Blaise
    Mendimi, Joseph-Marie N.
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Troye Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Antenatal care visit attendance, intermittent preventive treatment during pregnancy (IPTp) and malaria parasitaemia at delivery2014Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 13, s. 162-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The determinants and barriers for delivery and uptake of IPTp vary with different regions in sub-Saharan Africa. This study evaluated the determinants of ANC clinic attendance and IPTp-SP uptake among parturient women from Mount Cameroon Area and hypothesized that time of first ANC clinic attendance could influence uptake of IPTp-SP/dosage and consequently malaria parasite infection status at delivery. Methods: Two cross sectional surveys were carried out at the Government Medical Centre in the Mutengene Health Area, Mt Cameroon Area from March to October 2007 and June 2008 to April 2009. Consented parturient women were consecutively enrolled in both surveys. In 2007, socio-demographic data, ANC clinic attendance, gestational age, fever history and reported use/dosage of IPTp-SP were documented using a structured questionnaire. In the second survey only IPT-SP usage/dosage was recorded. Malaria parasitaemia at delivery was determined by blood smear microscopy and placental histology. Results and discussion: In 2007, among the 287 women interviewed, 2.2%, 59.7%, and 38.1% enrolled in the first, second and third trimester respectively. About 90% of women received at least one dose SP but only 53% received the two doses in 2007 and by 2009 IPTp-two doses coverage increased to 64%. Early clinic attendance was associated (P = 0.016) with fever history while being unmarried (OR = 2.2; 95% CI: 1.3-3.8) was significantly associated with fewer clinic visits (<4visits). Women who received one SP dose (OR = 3.7; 95% CI: 2.0-6.8) were more likely not to have attended >= 4visits. A higher proportion (P < 0.001) of women with first visit during the third trimester received only one dose, meanwhile, those who had an early first ANC attendance were more likely (OR = 0.4; 95% CI = 0.2 - 0.7) to receive two or more doses. Microscopic parasitaemia at delivery was frequent (P = 0.007) among women who enrolled in the third trimester and had received only one SP dose than in those with two doses. Conclusion: In the study area, late first ANC clinic enrolment and fewer clinic visits may prevent the uptake of two SP doses and education on early and regular ANC clinic visits can increase IPTp coverage.

  • 5. Anchang-Kimbi, Judith K
    et al.
    Achidi, Eric A
    Nkegoum, Blaise
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women.2009Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 8, s. 126-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated. METHOD: In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for P. falciparum in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded. RESULTS: Among these women, P. falciparum infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4%) than placental blood film (41.5%) and peripheral blood (8.0%) microscopy. In multivariate analysis, age (< or = 20 years old) (OR = 4.61, 95% CI = 1.47 - 14.70), history of fever attack (OR = 2.98, 95% CI = 1.58 - 5.73) were significant risk factors associated with microscopically detected parasitaemia. The use of > or = 2 SP doses (OR = 0.18, 95% CI = 0.06 - 0.52) was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years) (OR = 0.34, 95% CI = 0.15 - 0.75) was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33-5.62) was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia. CONCLUSION: Placenta histological examination was the most sensitive indicator of malaria infection at delivery. Microscopically detected parasitaemia was associated with increased risk of maternal anaemia at delivery, but not low-grade parasitaemia detected by placental histology only.

  • 6. Anchang-Kimbi, Judith K.
    et al.
    Achidi, Eric Akum
    Nkegoum, Blaise
    Mendimi, Joseph-Marie N.
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    IgG isotypic antibodies to crude Plasmodium falciparum blood-stage antigen associated with placental malaria infection in parturient Cameroonian women2016Inngår i: African Health Sciences, ISSN 1680-6905, E-ISSN 1729-0503, Vol. 16, nr 4, s. 1007-1017Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Few studies have reported an association between placental malaria (PM) infection and levels of isotypic antibodies against non-pregnancy associated antigens. Objective: To determine and evaluate IgG isotypic antibody levels to crude P. falciparum blood stage in women with and without PM infection. Methods: Levels of IgG (IgG1-IgG4) and IgM to crude P. falciparum blood stage antigen were measured by ELISA in 271 parturient women. Placental malaria infection was determined by placental blood microscopy and placental histology. Age, parity and intermittent preventive treatment during pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) usage were considered during analysis. Results: P. falciparum-specific IgG1 (96.5%) and IgG3 (96.7%) antibodies were predominant compared with IgG2 (64.6%) and IgG4 (49.1%). Active PM infection was associated with significant increased levels of IgG1, IgG4 and IgM while lower levels of these antibodies were associated with uptake of two or more IPTp-SP doses. PM infection was the only independent factor associated with IgG4 levels. Mean IgG1 + IgG3/IgG2 + IgG4 and IgG1 + IgG2 + IgG3/IgG4 ratios were higher among the PM-uninfected group while IgG4/IgG2 ratio prevailed in the infected group. Conclusion: PM infection and IPTp-SP dosage influenced P. falciparum-specific isotypic antibody responses to blood stage antigens. An increase in IgG4 levels in response to PM infection is of particular interest.

  • 7.
    Arama, Charles
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Assefaw-Redda, Y.
    Rodriguez, A.
    Fernández, C.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Corradin, G.
    Kaufmann, S. H.
    Reece, S. T.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Heterologous prime–boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guérin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c miceManuskript (preprint) (Annet vitenskapelig)
  • 8.
    Arama, Charles
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Assefaw-Redda, Yohannes
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Rodriguez, Ariane
    Fernández, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Corradin, Giampietro
    Kaufmann, Stefan H. E.
    Reece, Stephen T.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guerin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice2012Inngår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, nr 27, s. 4040-4045Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines. Results: In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-gamma and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses. Conclusion: The increased IFN-gamma-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.

  • 9.
    Arama, Charles
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Giusti, Pablo
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Boström, Stephanie
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Varani, Stefania
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Troye Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 3, s. e18319-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.

  • 10. Arama, Charles
    et al.
    Maiga, Bakary
    Dolo, Amagana
    Kouriba, Bourema
    Traore, Boubacar
    Crompton, Peter D.
    Pierce, Susan K.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Miller, Louis H.
    Doumbo, Ogobara K.
    Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?2015Inngår i: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 146, s. 152-156Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    There are many fundamental aspects of the immunobiology of Plasmodium falciparum infections that are not fully understood, therefore limiting our comprehension of how people become immune to malaria and why some ethnic groups living in malaria endemic areas are less susceptible than others. The complexity of parasite-host interactions and the genetic diversity of the parasites as well as the human host complicate our strategy to address this issue. In this mini-review we discuss and summarize what we have learned about African ethnic differences in susceptibility to malaria from immuno-epidemiological studies. Additionally, we suggest research topics that might be of great value for dissecting the mechanisms of protection by providing new insights into molecular interactions between the parasite and the host.

  • 11. Arama, Charles
    et al.
    Quin, Jaclyn E.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Kouriba, Bourema
    Östlund Farrants, Ann-Kristin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Doumbo, Ogobara K.
    Epigenetics and Malaria Susceptibility/Protection: A Missing Piece of the Puzzle2018Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, artikkel-id 1733Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    A better understanding of stable changes in regulation of gene expression that result from epigenetic events is of great relevance in the development of strategies to prevent and treat infectious diseases. Histone modification and DNA methylation are key epigenetic mechanisms that can be regarded as marks, which ensure an accurate transmission of the chromatin states and gene expression profiles over generations of cells. There is an increasing list of these modifications, and the complexity of their action is just beginning to be understood. It is clear that the epigenetic landscape plays a fundamental role in most biological processes that involve the manipulation and expression of DNA. Although the molecular mechanism of gene regulation is relatively well understood, the hierarchical order of events and dependencies that lead to protection against infection remain largely unknown. In this review, we propose that host epigenetics is an essential, though relatively under studied, factor in the protection or susceptibility to malaria.

  • 12. Arama, Charles
    et al.
    Skinner, Jeff
    Doumtabe, Didier
    Portugal, Silvia
    Tran, Tuan M.
    Jain, Aarti
    Traore, Boubacar
    Doumbo, Ogobara K.
    Davies, David Huw
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Dolo, Amagana
    Felgner, Philip L.
    Crompton, Peter D.
    Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens2015Inngår i: Open forum infectious diseases, ISSN 2328-8957, Vol. 2, nr 3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to < 0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig) M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.

  • 13.
    Arama, Charles
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Sciences Techniques and Technologies of Bamako, Mali.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    The path of malaria vaccine development: challenges and perspectives2014Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 5, s. 456-466Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Malaria is a life-threatening disease caused by parasites of the Plasmodium genus. In many parts of the world, the parasites have developed resistance to a number of antimalarial agents. Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies, use of insecticidal nets by individuals at risk and active research into malaria vaccines. Protection against malaria through vaccination was demonstrated more than 30years ago when individuals were vaccinated via repeated bites by Plasmodium falciparum-infected and irradiated but still metabolically active mosquitoes. However, vaccination with high doses of irradiated sporozoites injected into humans has long been considered impractical. Yet, following recent success using whole-organism vaccines, the approach has received renewed interest; it was recently reported that repeated injections of irradiated sporozoites increased protection in 80 vaccinated individuals. Other approaches include subunit malaria vaccines, such as the current leading candidate RTS,S (consisting of fusion between a portion of the P.falciparum-derived circumsporozoite protein and the hepatitis B surface antigen), which has been demonstrated to induce reasonably good protection. Although results have been encouraging, the level of protection is generally considered to be too low to achieve eradication of malaria. There is great interest in developing new and better formulations and stable delivery systems to improve immunogenicity. In this review, we will discuss recent strategies to develop efficient malaria vaccines.

  • 14.
    Arama, Charles
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Waseem, Shahid
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Fernández, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Assefaw-Redda, Yohannes
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    You, Liya
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Rodriguez, Ariane
    Radošević, Katarina
    Goudsmit, Jaap
    Kaufmann, Stefan H E
    Reece, Stephen T
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    A recombinant Bacille Calmette-Guerin construct expressing the Plasmodium falciparum circumsporozoite protein enhances dendritic cell activation and primes for circumsporozoite-specific memory cells in BALB/c mice2012Inngår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, nr 37, s. 5578-5584Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A protective malaria vaccine may induce both high levels of neutralising antibodies and strong T-cell responses. The Plasmodium falciparum circumsporozoite protein (CSp) is a leading pre-erythrocytic vaccine candidate. CSp is a week immunogen per se, but Mycobacterium bovis Bacille Calmette-Guérin (BCG) has excellent adjuvant activity and has been utilized as a vector to deliver heterologous vaccine candidate antigens. It is safe in immunocompetent individuals and inexpensive to produce. We assessed in vitro and in vivo a recombinant BCG-expressing CSp (BCG-CS) as malaria vaccine candidate. Immunisation of BALB/c mice with BCG-CS augmented numbers of dendritic cells (DCs) in draining lymph nodes and in the spleen. The activation markers MHC-class-II, CD40, CD80 and CD86 on DCs were significantly upregulated by BCG-CS as compared to wild-type BCG (wt-BCG). In vitro stimulation of bone marrow-derived DCs and macrophages with BCG-CS induced IL-12 and TNF-α production. BCG-CS induced higher phagocytic activity in macrophages as compared to wt-BCG. Immunogenicity studies show that BCG-CS induced CS-specific antibodies and IFN-γ-producing memory cells. In conclusion, BCG-CS is highly efficient in activating antigen-presenting cells (APCs) for priming of adaptive immunity. Implications for the rational design of novel vaccines against malaria and TB, the two major devastating poverty-related diseases, are discussed.

  • 15. Arkestål, Kurt
    et al.
    Sibanda, Elopy
    Thors, Cecilia
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Mduluza, Takafira
    Valenta, Rudolf
    Grönlund, Hans
    van Hage, Marianne
    Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-alpha 1,3-galactose2011Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 127, nr 4, s. 1024-1028Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The carbohydrate epitope galactose-alpha 1,3galactose (a-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that alpha-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). Objective: We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and a-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. Methods: Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with a-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and alpha-Gal was analyzed by means of ELISA. Results: Among the 47 parasite-infected patients, 85% had IgE antibodies against alpha-Gal (OD; median, 0.175; range, 0.1021.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.1031.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and a-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and alpha-Gal (P <. 001). Among the group with cat allergy, only 5 patients had IgE to alpha-Gal, and nearly 75% (n 5 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kUA/ L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P <.05) but no correlation between CDE and Fel d 5 and alpha-Gal. Conclusion: IgE to alpha-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/ allergy in parasite-infested areas.

  • 16.
    Awah, Nancy
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Balogun, Halima
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Achidi, E.
    Mariuba, L. A.
    Nogueira, P. A.
    Orlandi, P.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Gysin, J.
    Berzins, Klavs
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian children2011Inngår i: Parasite immunology (Print), ISSN 0141-9838, E-ISSN 1365-3024, Vol. 33, nr 2, s. 104-115Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have implicated reactive antibodies to the low molecular weight rhoptry-associated proteins (RAP-1, RAP-2/RSP-2 and RAP-3) in erythroid cell destruction during Plasmodium falciparum infection. In this pilot study, the frequency, specificity and functional capacity of naturally acquired anti-RAP-2/RSP-2 antibodies were investigated in the sera of anaemic and nonanaemic malaria-infected Cameroonian children. All sera recognized RAP-2/RSP-2 by FACS, irrespective of the clinical status of the subjects. However, the anaemic children showed higher levels of IgG antibodies than the nonanaemic group, while both groups showed similar levels of IgM antibodies. Only few individuals had detectable levels of RAP-2/RSP-2-specific IgG1 and IgG3 subclass antibodies, while no IgG2 and IgG4 subclass antibodies were detected in these subjects. By ELISA, the anaemic group tended to show higher levels of antibodies to RAP-2/RSP-2 regarding all antibody classes tested, except for IgG4 and IgE. Unexpectedly, sera from the nonanaemic group activated complement to a greater extent than those from the anaemic group. These results need to be confirmed in extended studies but indicate that the effector functions of the RAP-2/RSP-2-reactive antibodies may be more important than their amounts. Such antibodies could play a role in both immunity and pathogenesis during P. falciparum infection.

  • 17.
    Awah, Nancy W.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Berzins, Klavs
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Gysin, Jürg
    Unité de Parasitologie Expérimentale, URA Institut Pasteur/Univ-Med.
    Mechanisms of malarial anaemia: potential involvement of the Plasmodium falciparum low molecular weight rhoptry-associated proteins.2009Inngår i: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 112, nr 3, s. 295-302Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plasmodium falciparum malaria is a major cause of morbidity and mortality throughout the tropics. Anaemia is a constant feature of the disease. Pregnant women mostly primigravidae and children below the age of 5 years are the most afflicted. Its pathogenesis is multifactorial and incompletely understood. Among several factors, the destruction of erythrocytes (RBCs) is the most frequently observed cause of severe malarial anaemia and the removal of non-parasitized RBCs (nEs) is thought to be the most important, accounting for approximately 90% of the reduction in haematocrit in acute malaria. Previous studies demonstrated that the tagging of nEs with the parasite antigen RAP-2 (rhoptry-associated protein-2; also designated RSP-2) due to either failed or aborted invasion by merozoites resulted in the destruction of these cells. In this study we further investigated the mechanisms mediating the destruction of nEs in the development of severe malarial anaemia and the possible involvement of RAP-2/RSP-2 and other members of the low molecular weight rhoptry complex (RAP-1: rhoptry-associated protein-1 and RAP-3: rhoptry-associated protein-3). Antibodies to the rhoptry-associated proteins were found to recognise the surface of nEs in a parasitaemia-dependent manner after merozoite release in P. falciparumin vitro cultures. These cells, as well as erythroblasts co-cultured with infected RBCs (IEs), could then be destroyed by either phagocytosis or lysis after complement activation. The ability of anti-rhoptry antibodies to mediate the destruction of RAP-2/RSP-2-tagged erythroblasts in the presence of effector cells was also investigated. Data obtained suggest that mouse monoclonal antibodies to the low molecular weight RAP proteins mediate the death of RAP-2/RSP-2-tagged erythroblasts on interaction with adherent monocytes. The mechanism of cell death is not yet fully known, but seems to involve primarily apoptosis. The above observations suggest that the antibody response against RAP-2/RSP-2 and other members of the complex could trigger the destruction of RAP-2/RSP-2-tagged host cells. Taken together it appears that during severe anaemia a defective bone marrow or dyserythropoiesis possibly due to erythroblast cell death, may overlap with the accelerated destruction of normal erythroid cells, either by opsonisation or complement activation further aggravating the anaemia which may become fatal. These observations could therefore have implications in the design, development and deployment of future therapeutic interventions against malaria.

  • 18.
    Bergvall-Kåreborn, Birgitta
    et al.
    Luleå tekniska universitet, Institutionen för ekonomi, teknik och samhälle, Innovation och Design.
    Holst, Marita
    Luleå tekniska universitet, Institutionen för system- och rymdteknik, CDT.
    Ståhlbröst, Anna
    Luleå tekniska universitet, Institutionen för ekonomi, teknik och samhälle, Innovation och Design.
    Concept design with a living lab approach2009Inngår i: 2009 42nd Hawaii International Conference on System Sciences: HICSS ; Waikoloa, Hawaii, 5 - 8 January 20 / [ed] Ralph H Sprague Jr, IEEE Communications Society, 2009, s. 1-10Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Living Labs is a rather new research area and phenomena that introduces new ways of managing innovation processes. The underlying idea is that people's ideas, experiences, and knowledge, as well as their daily needs of support from products, services, or applications, should be the starting point in innovation. This paper illuminates experiences and accumulated knowledge to the area of concept design in an innovation process within a Living Lab. FormIT, a methodology developed for innovation processes within Living Labs is introduced through an illustration of how it has been utilised in a case. The experiences and the method are related to characteristics of Living Labs, and the paper closes with some concluding remarks in relation to concept design in a Living Lab.

  • 19.
    Bergvall-Kåreborn, Birgitta
    et al.
    Luleå tekniska universitet, Institutionen för ekonomi, teknik och samhälle, Innovation och Design.
    Holst, Marita
    Luleå tekniska universitet, Institutionen för system- och rymdteknik, CDT.
    Ståhlbröst, Anna
    Creating a new leverage point for information systems development2008Inngår i: Designing information and organisations with a positive lens, Amsterdam: JAI Press Ltd, 2008, s. 75-95Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    We present a new approach that shifts the leverage point of information systems development from problem orientation to opportunity development. Our approach, entitled FormIT, employs a careful focus on enhanced user involvement, concentrating on users as human beings, and attention to users’ needs as opposed to system requirements. As theoretical and methodological foundations, we build on the 4-D cycle model of Appreciative Inquiry and current research on needfinding. Our field experience demonstrates that FormIT shifts the systems development process from being reactive to being proactive, and in turn, enables a smoother implementation of inevitable change, particularly radical change. Moreover, FormIT stimulates the generation of rich local knowledge and helps reveal deep insights into the development process and the overall organization.

  • 20. Bolad, Ahmed
    et al.
    Farouk, Salah E.
    Modiano, David
    Berzins, Klavs
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Israelsson, Elisabeth
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Dolo, Amagana
    Doumbo, Ogobara K.
    Nebié, Issa
    Maiga, Boubacar
    Kouriba, Bourema
    Luoni, Gaia
    Sirima, Bienveu Sodiomon
    Distinct interethnic differences in IgG class/subclass and IgM antibody responses to malaria antigens but not in IgG responses to non-malarial antigens in sympatric tribes living in West Africa2005Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, nr 4, s. 380-386Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The well-established relative resistance to malaria observed in the Fulani ascompared with other sympatric tribes in West Africa has been attributed totheir higher levels of serum immunoglobulin (Ig) G antibodies to malarialantigens. In this study, we confirm and extend the previous findings by analysesof the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies inasymptomatic individuals of different sympatric tribes in Burkina Faso(Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantlyhigher median concentrations of anti-malarial IgG and IgM antibodies thanthe sympatric tribes at both locations. Although the overall subclass pattern ofantibodies did not differ between the tribes, with IgG1 and IgG3 as dominant,the Fulani showed consistently significantly higher levels of these subclasses ascompared with those of the non-Fulani individuals. No significant differenceswere seen in the levels of total IgG between the tribes, but the Fulani showedsignificantly higher levels of total IgM than their neighbours in both countries.While the antibody levels to some nonmalarial antigens showed the same patternof differences seen for antibody levels to malaria antigens, no significant suchdifferences were seen with antibodies to other nonmalarial antigens. In conclusion,our results show that the Fulani in two different countries show higherlevels of anti-malarial antibodies than sympatric tribes, and this appears not tobe a reflection of a general hyper-reactivity in the Fulani.

  • 21.
    Boström, Stephanie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Giusti, Pablo
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Arama, Charles
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut. University of Bamako, Mali.
    Persson, Jan-Olov
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Dara, Victor
    Traore, Boubacar
    Dolo, Amagana
    Doumbo, Ogobara
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Changes in the levels of cytokines, chemokines and malaria specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali2012Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 11, s. 109-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap. Methods: Circulating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA. Results: The results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon. Conclusions: Taken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against P. falciparum parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.

  • 22.
    Boström, Stephanie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Schmiegelow, C.
    Abu Abed, U.
    Minja, D. T. R.
    Lusingu, J.
    Brinkmann, V.
    Honkpehedji, Y. J.
    Loembe, M. M.
    Adegnika, A. A.
    Mordmueller, B.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Amulic, B.
    Neutrophil alterations in pregnancy-associated malaria and induction of neutrophil chemotaxis by Plasmodium falciparum2017Inngår i: Parasite immunology (Print), ISSN 0141-9838, E-ISSN 1365-3024, Vol. 39, nr 6, artikkel-id UNSP e12433Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pregnancy-associated malaria (PAM) is a severe form of the disease caused by sequestration of Plasmodium falciparum-infected red blood cells (iRBCs) in the developing placenta. Pathogenesis of PAM is partially based on immunopathology, with frequent monocyte infiltration into the placenta. Neutrophils are abundant blood cells that are essential for immune defence but may also cause inflammatory pathology. Their role in PAM remains unclear. We analysed neutrophil alterations in the context of PAM to better understand their contribution to disease development. Pregnant women exposed to Plasmodium falciparum had decreased numbers of circulating neutrophils. Placental-like BeWo cells stimulated with malaria parasites produced the neutrophil chemoattractant IL-8 and recruited neutrophils in a trans-well assay. Finally, immunostaining of a PAM placenta confirmed neutrophil accumulation in the intervillous space. Our data indicate neutrophils may play a role in placental malaria and should be more closely examined as an etiological agent in the pathophysiology of disease.

  • 23.
    Boström, Stéphanie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Amulic, Borko
    Schmiegelow, Christentze
    Abed, Ulrike
    Minja, Daniel
    Lusingu, John
    Brinkmann, Volker
    Luty, Adrian
    Schwarzer, Evelin
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Neutrophil migration during placental malaria in vivo and in vitro and distinct neutrophil patterns induced by hemozoinManuskript (preprint) (Annet vitenskapelig)
  • 24.
    Boström, Stéphanie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Ibitokou, Samad
    Oesterholt, Mayke
    Schmiegelow, Christentze
    Persson, Jan-Olov
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Minja, Daniel
    Lusingu, John
    Lemnge, Martha
    Fievet, Nadine
    Deloron, Philippe
    Luty, Adrian J. F.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Biomarkers of Plasmodium falciparum infection during pregnancy in women living in Northeastern Tanzania2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 11, s. e48763-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In pregnant women, Plasmodium falciparum infections are an important cause of maternal morbidity as well as fetal and neonatal mortality. Erythrocytes infected by these malaria-causing parasites accumulate through adhesive interactions in placental intervillous spaces, thus evading detection in peripheral blood smears. Sequestered infected erythrocytes induce inflammation, offering the possibility of detecting inflammatory mediators in peripheral blood that could act as biomarkers of placental infection. In a longitudinal, prospective study in Tanzania, we quantified a range of different cytokines, chemokines and angiogenic factors in peripheral plasma samples, taken on multiple sequential occasions during pregnancy up to and including delivery, from P. falciparum-infected women and matched uninfected controls. The results show that during healthy, uninfected pregnancies the levels of most of the panel of molecules we measured were largely unchanged except at delivery. In women with P. falciparum, however, both comparative and longitudinal assessments consistently showed that the levels of IL-10 and IP-10 increased significantly whilst that of RANTES decreased significantly, regardless of gestational age at the time the infection was detected. ROC curve analysis indicated that a combination of increased IL-10 and IP-10 levels and decreased RANTES levels might be predictive of P. falciparum infections. In conclusion, our data suggest that host biomarkers in peripheral blood may represent useful diagnostic markers of P. falciparum infection during pregnancy, but placental histology results would need to be included to verify these findings.

  • 25.
    Bujila, Ioana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Chérif, Mariama
    Sanou, Guillaume S.
    Vafa, Manijeh
    O'Connell, Mary A.
    Ouédraogo, Issa N.
    Lennartsson, Andreas
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Östlund Farrants, Ann-Kristin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Transcriptome and DNA methylome analysis of two sympatric ethic groups with differential susceptibility to Plasmodium falciparum infection living in Burkina FasoManuskript (preprint) (Annet vitenskapelig)
  • 26.
    Bujila, Ioana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Rolicka, Anna
    Schwarzer, Evelin
    Skorokhod, Oleksii
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Östlund Farrants, Ann-Kristin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Exposure to Plasmodium falciparum-derived hemozoin leads to impairment of transcriptional activation upon dendritic cell maturationManuskript (preprint) (Annet vitenskapelig)
  • 27.
    Bujila, Ioana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Schwarzer, Evelin
    Skorokhod, Oleksii
    Weidner, Jessica M.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Östlund Farrants, Ann-Kristin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Malaria-derived hemozoin exerts early modulatory effects on the phenotype and maturation of human dendritic cells2016Inngår i: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 18, nr 3, s. 413-423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plasmodium falciparum (P. falciparum)-induced effects on the phenotype of human dendritic cells (DC) could contribute to poor induction of long-lasting protective immunity against malaria. DC ability to present antigens to naïve T cells, thus initiating adaptive immune responses depends on complex switches in chemokine receptors, production of soluble mediators and expression of molecules enabling antigen-presentation and maturation. To examine the cellular basis of these processes in the context of malaria, we performed detailed analysis of early events following exposure of human monocyte-derived DC to natural hemozoin (nHZ) and the synthetic analog of its heme core, β-hematin. DC exposed to either molecule produced high levels of the inflammatory chemokine MCP-1, showed continuous high expression of the inflammatory chemokine receptor CCR5, no upregulation of the lymphoid homing receptor CCR7 and no cytoskeletal actin redistribution with loss of podosomes. DC partially matured as indicated by increased expression of major histocompatibility complex (MHC) class II and CD86 following nHZ and β-hematin exposure, however there was a lack in expression of the maturation marker CD83 following nHZ but not β-hematin exposure. Overall our data demonstrate that exposure to nHZ partially impairs the capacity of DC to mature, an effect in part differential to β-hematin.

  • 28.
    Calla-Magarinos, Jacqueline
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi. National University Hospital of Iceland.
    Fernandez, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Freysdottir, Jona
    Alkaloids from Galipea longiflora Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4(+) T cells2013Inngår i: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 16, nr 1, s. 79-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alkaloids obtained from the plant Evanta have been shown to have dual effects in Leishmania infection; a direct leishmanicidal effect on the parasite and more importantly, the alkaloids affect both polyclonal and Leishmania-specific stimulation of T-cells. Dendritic cells (DCs) play a pivotal role in stimulation and polarization of naive T cells towards a Th1, Th2, Th17 or regulatory phenotype. In leishmaniasis, the interactions between the parasites and DCs are complex and involve contradictory functions that can stimulate or suppress T cell responses, leading to the control of infection or progression of disease. In this study the effect of an alkaloid extract of Evanta (AEE) or the purified alkaloid 2-phenilquinoline (2Ph) on the activation of human DCs and their ability to stimulate allogeneic CD4(+) T cells was analyzed. The expression of surface activation molecules was not affected on DCs stimulated in the presence of AEE or 2Ph nor did AEE-DCs or 2Ph-CDs affect the expression of activation surface molecules on allogeneic CD4(+) T cells. In contrast, as compared with control, the secretion of IL-12p40, IL-23 and IL-6 was lower from AEE-DCs and 2Ph-CDs and allogeneic CD4(+) T cells co-cultured with these DCs secreted lower levels of IFN-gamma and IL-10 but the same levels of IL-17. These results demonstrate that AEE and 2Ph affect the stimulation of DCs and their ability to stimulate allogeneic CD4(+) T cells by reducing the production of IFN-gamma, IL-12 p40, IL-6 and IL-23. This suggests that AEE and 2Ph may take part in regulation of inflammation.

  • 29.
    Calla-Magariños, Jacqueline
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Fernádez, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Freysdottir, Jona
    Alkaloids from Galipea longiflora Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4+ T cellsArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alkaloids obtained from the plant Evanta have been shown to have dual effects in Leishmania infection; a direct leishmanicidal effect on the parasite and more importantly, the alkaloids affect both polyclonal and Leishmania-specific stimulation of T-cells.  

    Dendritic cells (DCs) play a pivotal role in stimulation and polarization of naïve T cells towards a Th1, Th2, Th17 or regulatory phenotype. In leishmaniasis, the interactions between the parasites and DCs are complex and involve contradictory functions that can stimulate or suppress T cell responses, leading to the control of infection or progression of disease.

     In this study the effect of an alkaloid extract of Evanta (AEE) or the purified alkaloid 2-phenilquinoline (2Ph) on the activation of human DCs and their ability to stimulate allogeneic CD4+ T cells was analyzed. The expression of surface activation molecules was not affected on DCs stimulated in the presence of AEE or 2Ph nor did AEE-DCs or 2Ph-CDs affect the expression of activation surface molecules on allogeneic CD4+ T cells. In contrast, as compared with control, the secretion of IL-12p40, IL-23 and IL-6 was lower from AEE-DCs and 2Ph-CDs and allogeneic CD4+ T cells co-cultured with these DCs secreted lower levels of IFN-γ and IL-10 but the same levels of IL-17.

    These results demonstrate that AEE and 2Ph affect the stimulation of DCs and their ability to stimulate allogeneic CD4+ T cells by reducing the production of IFN-g, IL-12 p40, IL-6 and IL-23. This suggests that AEE and 2Ph may take part in regulation of inflammation.

  • 30.
    Calla-Magariños, Jacqueline
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Gimenez, A.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Fernandez, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    An alkaloid extract of Evanta, traditionally used as anti-Leishmania agent in Bolivia, inhibits cellular proliferation and interferon-g production in polyclonally activated cells2009Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, nr 3, s. 251-258Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traditional medicine and scientific studies have shown that the raw extract ofEvanta [Galipea longiflora, Angostura longiflora (Krause) Kallunki] exhibits antileishmanialactivity. We hypothesized that the healing observed when usingthis plant might not only be due to the direct action on the parasite, but possiblyto a parallel effect on the host immune response to the parasite involvedin the healing process. We show here that an alkaloid extract of Evanta (AEE)directly killed the parasite already at a dose of 10 lg ⁄ ml, but at this low concentration,AEE did not have a major effect on viability and proliferation ofeukaryotic cells. The whole extract was also found to be stronger than 2-phenylquinoline,the most prominent alkaloid in AEE. AEE was not directlystimulating B or T cells or J774 macrophages. However, it interfered with theactivation of both mouse and human T cells, as revealed by a reduction of invitro cellular proliferation and interferon-gamma (IFN-c) production. The effectwas more evident when the cells were pretreated with AEE and subsequentlystimulated with the polyclonal T-cell activators Concanavalin A and anti-CD3.Taken together, our results suggest that Evanta have a direct leishmanicidaleffect and due to the effect on IFN-c production it might contribute to controlthe chronic inflammatory reaction that characterize Leishmania infectionpathology, but in vivo studies are necessary to corroborate this finding.

  • 31.
    Calla-Magariños, Jacqueline
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Quispe, T.
    Giménez, A.
    Freysdottir, J.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Fernández, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Quinolinic Alkaloids from Galipea longiflora Krause Suppress Production of Proinflammatory Cytokines in vitro and Control Inflammation in vivo upon Leishmania Infection in Mice2013Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 77, nr 1, s. 30-38Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-γ production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-γ production (55% and 63% reduction compared to untreated cells, respectively). Apart from IFN-γ, the production of IL-12 and TNF was also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load as smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.

  • 32.
    Calla-Magariños, Jacqueline
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Quispe, Teddy
    Giménez, Alberto
    Freysdottir, Jona
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Fernández, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Quinolinic alkaloids from Galipea longiflora suppress inflammatory cytokine production in vitro and control inflammatory reaction in vivo upon Leishmania infectionInngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-g production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-g production (55 % and 63 % reduction compared to untreated cells, respectively). Apart from IFN-g, the production of IL-12 and TNF were also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load since smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.

  • 33. Cherif, M. K.
    et al.
    Sanou, G. S.
    Maiga, B.
    Israelsson, E.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Ouedraogo, A. L.
    Bougouma, E. C.
    Diarra, A.
    Ouedraogo, A.
    Ouattara, A. S.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Dolo, A.
    Cavanagh, D. R.
    Theisen, M.
    Modiano, D.
    Sirima, S. B.
    Nebie, I.
    Fc gamma RIIa Polymorphism and Anti-Malaria-Specific IgG and IgG Subclass Responses in Populations Differing in Susceptibility to Malaria in Burkina Faso2012Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 75, nr 6, s. 606-613Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fc?RIIa is known to be polymorphic; and certain variants are associated with different susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in Fc?RIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have addressed these questions in Burkina Faso. This study aimed to assess the influence of Fc?RIIa-R131H polymorphism on anti-falciparum malaria IgG and IgG subclass responses in the Fulani and the Mossi ethnic groups living in Burkina Faso. Healthy adults more than 20 years old belonging to the Mossi or the Fulani ethnic groups were enrolled for the assessment of selected parasitological, immunological and genetic variables in relation to their susceptibility to malaria. The prevalence of the Plasmodium falciparum infection frequency was relatively low in the Fulani ethnic group compared to the Mossi ethnic group. For all tested antigens, the Fulani had higher antibody levels than the Mossi group. In both ethnic groups, a similar distribution of Fc?RIIa R131H polymorphism was found. Individuals with the R allele of Fc?RIIa had higher antibody levels than those with the H allele. This study confirmed that malaria infection affected less the Fulani group than the Mossi group. Fc?RIIa-R131H allele distribution is similar in both ethnic groups, and higher antibody levels are associated with the Fc?RIIa R allele compared to the H allele.

  • 34. Cherif, Mariama
    et al.
    Amoako-Sakyi, Daniel
    Dolo, Amagana
    Pearson, Jan-Olov
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Gyan, Ben
    Obiri-Yeboah, Dorcas
    Nebie, Issa
    Sirima, Sodiomon B.
    Doumbo, Ogobara
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bakary, Maiga
    Distribution of Fc gamma R gene polymorphisms among two sympatric populations in Mali: differing allele frequencies, associations with malariometric indices and implications for genetic susceptibility to malaria2016Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 15, artikkel-id 29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genetic polymorphisms in the complex gene cluster encoding human Fc-gamma receptors (Fc gamma Rs) may influence malaria susceptibility and pathogenesis. Studying genetic susceptibility to malaria is ideal among sympatric populations because the distribution of polymorphic genes among such populations can help in the identification malaria candidate genes. This study determined the distribution of three FcyRs single nucleotide polymorphisms (SNPs) (Fc gamma RIIB-rs1050519, Fc gamma RIIC-rs3933769 and Fc gamma RIIIA-rs396991) among sympatric Fulani and Dogon children with uncomplicated malaria. The association of these SNPs with clinical, malariometric and immunological indices was also tested. Methods: This study involved 242 Fulani and Dogon volunteers from Mali age under 15 years. All SNPs were genotyped with predesigned TaqMan (R) SNP Genotyping Assays. Genotypic and allelic distribution of SNPs was compared across ethnic groups using the Fisher exact test. Variations in clinical, malariometric and immunologic indices between groups were tested with Kruskal-Wallis H, Mann-Whitney U test and Fisher exact test where appropriate. Results: The study confirmed known malariometric and immunologic differences between sympatric Fulani and non-Fulani tribes. Parasite density was lower in the Fulani than the Dogon (p < 0.0001). The mutant allele of Fc gamma RIIC (rs3933769) was found more frequently in the Fulani than the Dogon (p < 0.0001) while that of Fc gamma RIIIA (rs396991) occurred less frequently in the Fulani than Dogon (p = 0.0043). The difference in the mutant allele frequency of Fc gamma RIIB (rs1050519) between the two ethnic groups was however not statistically significant (p = 0.064). The mutant allele of rs396991 was associated with high malaria-specific IgG1 and IgG3 in the entire study population and Dogon tribe, p = 0.023 and 0.015, respectively. Parasite burden was lower in carriers of the Fc gamma RIIC (rs3933769) mutant allele than non-carriers in the entire study population (p < 0.0001). Carriers of this allele harboured less than half the parasites found in non-carriers. Conclusion: Differences in the allelic frequencies of rs3933769 and rs396991 among Fulani and Dogon indirectly suggest that these SNPs may influence malaria susceptibility and pathogenesis in the study population. The high frequency of the Fc gamma RIIC (rs3933769) mutant allele in the Fulani and its subsequent association with low parasite burden in the entire study population is noteworthy.

  • 35. Cherif, Mariama K.
    et al.
    Sanou, Guillaume S.
    Bougouma, Edith C.
    Diarra, Amidou
    Ouedraogo, Alphonse
    Dolo, Amagana
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cavanagh, David R.
    Theisen, Michael
    Modiano, David
    Sirima, Sodiomon B.
    Nebie, Issa
    Is Fc gamma receptor IIA (Fc gamma RIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?2015Inngår i: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 142, s. 41-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study, the influences of Fc gamma RIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up for 5 months through the high transmission season to assess the parasitological, immunological and genetic endpoints in relation to clinical malaria status. There was a similar distribution of homozygous and heterozygous individuals carrying the Fc gamma RIIA-131R/R and Fc gamma RIIA-131R/H allele, whereas the number of Fc gamma RIIA-131H/H homozygous individuals was lower. P. falciparum infection frequency was not associated with the Fc gamma RIIa-131R/H polymorphism. Only IgG antibody responses to GLURP R0 showed a significant association between antibody levels and Fc gamma RIIA polymorphism (p = 0.02). IgG levels to MSP2a were significantly higher in children who did not experience any clinical malaria episode compared to those who experienced at least one malaria episode (p = 0.019). Cytophilic and non-cytophylic IgG subclass levels were higher in children without malaria than those who experienced at least one malaria episode. This difference was statistically significant for IgG1 to MSP3 (p = 0.003) and to MSP2a (p = 0.006); IgG3 to MSP2a (p = 0.007) and to GLURP R0 (p = 0.044); IgG2 to MSP2b (p = 0.007) and IgG4 to MSP3 (p = 0.051) and to MSP2a (p = 0.049). In this study, homozygous carriers of the Fc gamma RIIA-131R/R allele had higher malaria-specific antibody levels compare to the heterozygous carriers Fc gamma RIIA-131R/H alleles and to homozygous carriers of Fc gamma RIIA-131H/H alleles. The pre-existing antibodies responses were related to a reduced subsequent risk of clinical malaria.

  • 36.
    Chochliouros, Joannis
    et al.
    aHellenic Telecommunications Organization, S.A. (OTE).
    Ziegler, Sébastien
    Mandat International.
    Alonistioti, Nancy
    Istituto Italiano Privacy.
    Stamatelatos, Makis
    National and Kapodistrian University of Athens.
    Kontopoulos, Panagiotis
    National and Kapodistrian University of Athens.
    Mourikas, George
    HW Communications, United Kingdom.
    Vlachos, Vasileios
    Comp. Technology Institute and Press and Technological Educational Insti-Tute of Thessaly.
    Gliguric, Nenad
    DunavNet, Greece.
    Holst, Marita
    Luleå tekniska universitet, Institutionen för system- och rymdteknik, CDT.
    Enabling crowd-sourcing-based privacy risk assessment in EU: the privacy flag project2017Inngår i: PCI 2017: Proceedings of the 21st Pan-Hellenic Conference on Informatics, New York: ACM Digital Library, 2017, Vol. F132523, artikkel-id 31Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Personal data have become merchandisable asset encouraging stakeholders to collect and trade them without end-user's awareness and acceptance. Although EU is adapting the legal framework, the extent of applications most of which are developed from outside the EU jurisdiction, strongly limit the possibility to effectively impose a privacy-protection framework globally. The Privacy Rag project researches and combines the potential of crowds ourcing, ICT technologies and legal expertise for enabling citizens monitoring and controlling their privacy1.

  • 37. Chuangchaiya, S
    et al.
    Jangpatarapongsa, K
    Chootong, P
    Sirichaisinthop, J
    Sattabongkot, J
    Pattanapanyasat, K
    Chotivanich, K
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Cui, L
    Udomsangpetch, R
    Immune response to Plasmodium vivax has a potential to reduce malaria severity2010Inngår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 160, nr 2, s. 233-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Summary Plasmodium falciparum infection causes transient immunosuppression during the parasitaemic stage. However, the immune response during simultaneous infections with both P. vivax and P. falciparum has been investigated rarely. In particular, it is not clear whether the host's immune response to malaria will be different when infected with a single or mixed malaria species. Phenotypes of T cells from mixed P. vivax-P. falciparum (PV-PF) infection were characterized by flow cytometry, and anti-malarial antibodies in the plasma were determined by an enzyme-linked immunosorbent assay. We found the percentage of CD3(+)delta2(+)-T cell receptor (TCR) T cells in the acute-mixed PV-PF infection and single P. vivax infection three times higher than in the single P. falciparum infection. This implied that P. vivax might lead to the host immune response to the production of effector T killer cells. During the parasitaemic stage, the mixed PV-PF infection had the highest number of plasma antibodies against both P. vivax and P. falciparum. Interestingly, plasma from the group of single P. vivax or P. falciparum malaria infections had both anti-P. vivax and anti-P. falciparum antibodies. In addition, antigenic cross-reactivity of P. vivax or P. falciparum resulting in antibodies against both malaria species was shown in the supernatant of lymphocyte cultures cross-stimulated with either antigen of P. vivax or P. falciparum. The role of delta2 +/- TCR T cells and the antibodies against both species during acute mixed malaria infection could have an impact on the immunity to malaria infection.

  • 38. Costa, Giulia
    et al.
    Loizon, Séverine
    Guenot, Marianne
    Mocan, Iulia
    Halary, Franck
    de Saint-Basile, Geneviève
    Pitard, Vincent
    Déchanet-Merville, Julie
    Moreau, Jean-François
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Mercereau-Puijalon, Odile
    Behr, Charlotte
    Control of Plasmodium falciparum erythrocytic cycle: gamma-delta T cells target the red blood cell-invasive merozoites2011Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 26, s. 6952--6962Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The control of Plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, as it prevents pathogenesis and progression towards severe disease. P.falciparum blood-stage parasite cultures are inhibited by human Vγ9Vδ2 gamma-delta T cells, but the underlying mechanism remains poorly understood. Here, we show that both intra-erythrocytic parasites and the extracellular red blood cell-invasive merozoites specifically activate Vγ9Vδ2 T cells in a γδ T cell receptor dependent manner and trigger their degranulation. In contrast, the γδ T cell-mediated anti-parasitic activity only targets the extracellular merozoites. Using perforin-deficient and granulysin-silenced T cell lines, we demonstrate that granulysin is essential for the in vitro anti-plasmodial process, whereas perforin is dispensable. Patients infected with P.falciparum exhibited elevated granulysin plasma levels associated with high levels of granulysin-expressing Vδ2(+) T cells endowed with parasite-specific degranulation capacity. This indicates in vivo activation of Vγ9Vδ2 T cells along with granulysin triggering and discharge during primary acute falciparum malaria. Altogether, this work identifies Vγ9Vδ2 T cells as unconventional immune effectors targeting the red blood cell-invasive extracellular P.falciparum merozoites and opens novel perspectives for immune interventions harnessing the anti-parasitic activity of Vγ9Vδ2 T cells to control parasite density in malaria patients.

  • 39. Courtin, David
    et al.
    Milet, Jacqueline
    Bertin, Gwladys
    Vafa, Manijeh
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Sarr, Jean Birame
    Watier, Laurence
    Deloron, Philippe
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Garcia, André
    Migot-Nabias, Florence
    G6PD A-variant influences the antibody responses to Plasmodium falciparum MSP2.2011Inngår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, nr 6, s. 1287-1292Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, α(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A- carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cell-mediated immune activity may explain the clinical protection afforded by this genetic trait.

  • 40. Curbo, Sophie
    et al.
    Gaudin, Raphael
    Carlsten, Mattias
    Malmberg, Karl-Johan
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Ahlborg, Niklas
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Karlsson, Anna
    Johansson, Magnus
    Lundberg, Mathias
    Regulation of interleukin-4 signaling by extracellular reduction of intramolecular disulfides2009Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 390, nr 4, s. 1272-1277Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Interleukin-4 (IL-4) contains three structurally important intramolecular disulfides that are required for the bioactivity of the cytokine. We show that the cell surface of HeLa cells and endotoxin-activated monocytes can reduce IL-4 intramolecular disulfides in the extracellular space and inhibit binding of IL-4 to the IL-4R alpha receptor. IL-4 disulfides were in vitro reduced by thioredoxin 1 (Trx1) and protein disulfide isomerase (PDI). Reduction of IL-4 disulfides by the cell surface of HeLa cells was inhibited by auranofin, an inhibitor of thioredoxin reductase that is an electron donor to both Trx1 and PDI. Both Trx1 and PDI have been shown to be located at the cell surface and our data suggests that these enzymes are involved in catalyzing reduction of IL-4 disulfides. The pro-drug N-acetylcysteine (NAC) that promotes T-helper type 1 responses was also shown to mediate the reduction of IL-4 disulfides. Our data provides evidence for a novel redox dependent pathway for regulation of cytokine activity by extracellular reduction of intramolecular disulfides at the cell surface by members of the thioredoxin enzyme family. 

  • 41.
    Danielsson, Marita
    Karlstads universitet.
    Fingerräkning: Lärarerns roll och betydelse för att ge elever en god taluppfattning2008Independent thesis Basic level (university diploma), 15 poäng / 22,5 hpOppgave
    Abstract [en]

     

    Abstract

    The aim of this essay is to look into how teachers view pupils who use finger arithmetic

    during mathematic classes. How do these teachers help them to move on with their learning,

    what information and problem-solving material do they use?

    I made qualitative interviews with grade two- and grade three teachers, in three schools.

    The interviews showed that the teachers find it difficult to adopt a suitable attitude towards

    finger arithmetic. In addition, lack of time for planning and lack of knowledge about various

    experimental methods caused further predicaments. The teachers were aware that arithmetic

    experimental material was attainable at the schools, but time to learn about it and how to use

    it was lacking. Time shortage made the teachers relay on traditional textbooks and teaching

    aids available for each grade. The fact that teachers have different knowledge and various

    views on the understanding of numbers also emerged.

  • 42. Dolo, A
    et al.
    Coulibaly, M
    Maïga, B
    Daou, M
    Arama, C
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Troye-Blomberg, M
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Doumbo, O
    Réponse humorale anti-Plasmodium falciparum AMA1 et MSP1 dans deux groupes ethniques vivant en sympatrie au Mali: [Humoral immune anti-Plasmodium falciparum AMA1 and MSP1 response in two ethnic groups living in sympatry in Mali].2012Inngår i: Bulletin de la Société de Pathologie Exotique, ISSN 0037-9085, E-ISSN 1961-9049, Vol. 105, nr 5, s. 364-369Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fulani of Mali are known for their lower susceptibility to Plasmodium falciparum malaria than their neighbours, the Dogon, despite similar transmission conditions. However, the mechanisms underlying these differences are poorly understood, particularly those concerning antigenspecific immune responses. The Apical Membrane Antigen 1 (AMA1) and the Merozoite Surface Antigen 1 (MSP1) are two malaria vaccine candidates, which play a pivotal role during the invasion of parasites into erythrocytes, and in the case of AMA1, of hepatocytes. Therefore, we analyzed the level of anti-AMA1 and anti-MSP1 antibodies (FVO and 3D7 alleles), by using ELISA (Enzyme Linked Immuno Sorbent Assay) to investigate whether there are differences between the two ethnic groups. Our results show that the splenic rate, the level of anti-AMA1 and anti-MSP1 were significantly higher in Fulani compared to Dogon; while the parasite rate was lower in Fulani group compared to Dogon. Our results suggest that the lower susceptibility of Fulani to malaria could be due to the higher specific humoral responses against AMA1 and MSP 1 in Fulani's ethnic group compared to Dogon.

  • 43. Dorlo, Thomas P. C.
    et al.
    Fernández, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    De Vries, Peter J.
    Boraschi, Diana
    Mbacham, Wilfred F.
    Poverty-Related Diseases College: a virtual African-European network to build research capacity2016Inngår i: BMJ global health, ISSN 2059-7908, Vol. 1, nr 1, artikkel-id e000032Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Poverty-Related Diseases College was a virtual African-European college and network that connected young African and European biomedical scientists working on poverty-related diseases. The aim of the Poverty-Related Diseases College was to build sustainable scientific capacity and international networks in poverty-related biomedical research in the context of the development of Africa. The Poverty-Related Diseases College consisted of three elective and mandatory training modules followed by a reality check in Africa and a science exchange in either Europe or the USA. In this analysis paper, we present our experience and evaluation, discuss the strengths and encountered weaknesses of the programme, and provide recommendations to policymakers and funders.

  • 44.
    Edzen, Svante
    et al.
    Luleå tekniska universitet, Institutionen för system- och rymdteknik, Datavetenskap.
    Holst, Marita
    Sandström, Annica
    Luleå tekniska universitet, Institutionen för ekonomi, teknik och samhälle, Samhällsvetenskap.
    Answers to questions about ”The Creative University”2004Rapport (Annet vitenskapelig)
    Abstract [en]

    As part of the evaluation of ”The Creative University” a questionnaire was sent out to all employees of Luleå University of Technology, during May 2002. The three PhD students who are connected to the evaluation prepared the questionnaire. The purpose of the questionnaire was to gain answers to questions posed about three main areas: The employees participation in the work process, the attitudes of the employees about the contents of the new vision and what shape the communication and meetings between employees has taken. In addition to the introductory background questions, the questionnaire was divided into three parts. The three main areas of the investigation were more or less covered in the three parts of the questionnaire. The first part was in reference to the development work done in the first phase, in which the objectives and the vision of the “Creative University” were formulated. The second part of the questionnaire was about the implementation of the new strategy, a process that is still in progress at the university. The questionnaire was divided into different parts in order to see if there was any difference in the pattern of participation for the different phases. In the second part there were also questions pertaining to the availability of information and to what degree the employees cooperate across boarders. Moreover, the respondents were asked to give an account of their views on how they regard the concept of “Integrated Knowledge Building”. The questionnaire ended with a third part in which the respondents were asked to respond to a number of statements about the contents of the vision and it’s implementation. The collective impressions can be said to be that employees of the University have been informed about the contents of the new vision. The goals of the vision receive support, such as recruiting more students, cooperating interdisciplinary, and an increased contact with the surrounding society. However, there appears to be no collective view of the concept of ”Integrated Knowledge Building”. As a last comment the compilation of the results show that many employees do not feel part of the implementation. The process of change has not affected the daily work for the majority of employees

  • 45. Ferwerda, Bart
    et al.
    Alonso, Santos
    Banahan, Kathy
    McCall, Matthew B B
    Giamarellos-Bourboulis, Evangelos J
    Ramakers, Bart P
    Mouktaroudi, Maria
    Fain, Pamela R
    Izagirre, Neskuts
    Syafruddin, Din
    Cristea, Tudor
    Mockenhaupt, Frank P
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Kumpf, Oliver
    Maiga, Boubacar
    Dolo, Amagana
    Doumbo, Ogobara
    Sundaresan, Santhosh
    Bedu-Addo, George
    van Crevel, Reinout
    Hamann, Lutz
    Oh, Djin-Ye
    Schumann, Ralf R
    Joosten, Leo A B
    de la Rúa, Concepcion
    Sauerwein, Robert
    Drenth, Joost P H
    Kullberg, Bart-Jan
    van der Ven, André J A M
    Hill, Adrian V
    Pickkers, Peter
    van der Meer, Jos W M
    O'Neill, Luke A J
    Netea, Mihai G
    Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock.2009Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, nr 25, s. 10272-10277Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adequate responses by our innate immune system toward invading pathogens were of vital importance for surviving infections, especially before the antibiotic era. Recently, a polymorphism in Mal (Ser180Leu, TIRAP rs8177374), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, has been described to provide protection against a broad range of infectious pathogens. We assessed the functional effects of this polymorphism in human experimental endotoxemia, and we demonstrate that individuals bearing the TIRAP 180L allele display an increased, innate immune response to TLR4 and TLR2 ligands, but not to TLR9 stimulation. This phenotype has been related to an increased resistance to infection. However, an overshoot in the release of proinflammatory cytokines by TIRAP 180L homozygous individuals suggests a scenario of balanced evolution. We have also investigated the worldwide distribution of the Ser180Leu polymorphism in 14 populations around the globe to correlate the genetic makeup of TIRAP with the local infectious pressures. Based on the immunological, clinical, and genetic data, we propose that this mutation might have been selected in West Eurasia during the early settlement of this region after the out-of-Africa migration of modern Homo sapiens. This combination of functional and genetic data provides unique insights to our understanding of the pathogenesis of sepsis.

  • 46. Fievet, Nadine
    et al.
    Varani, Stefania
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Ibitokou, Samad
    Briand, Valerie
    Louis, Stephanie
    Perrin, Rene Xavier
    Massougbogji, Achille
    Hosmalin, Anne
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Deloron, Philippe
    Plasmodium falciparum exposure in utero, maternal age and parity influence the innate activation of foetal antigen presenting cells2009Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 8, s. 251-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Malaria in pregnancy is associated with immunological abnormalities in the newborns, such as hampered T-helper 1 responses and increased T-regulatory responses, while the effect of maternal Plasmodium falciparum infection on foetal innate immunity is still controversial. Materials and methods: The immunophenotype and cytokine release by dendritic cells (DC) and monocytes were evaluated in cord blood from 59 Beninese women with or without malaria infection by using flow cytometry. Results: Accumulation of malaria pigment in placenta was associated with a partial maturation of cord blood myeloid and plasmacytoid DC, as reflected by an up-regulated expression of the major histocompatibility complex class II molecules, but not CD86 molecules. Cells of newborns of mothers with malaria pigment in their placenta also exhibited significantly increased cytokine responses upon TLR9 stimulation. In addition, maternal age and parity influenced the absolute numbers and activation status of cord blood antigen-presenting cells. Lastly, maternal age, but not parity, influenced TLR3, 4 and 9 responses in cord blood cells. Discussion: Our findings support the view that placental parasitization, as indicated by the presence of malaria pigment in placental leukocytes, is significantly associated with partial maturation of different DC subsets and also to slightly increased responses to TLR9 ligand in cord blood. Additionally, other factors, such as maternal age and parity should be taken into consideration when analysing foetal/neonatal innate immune responses. Conclusion: These data advocate a possible mechanism by which PAM may modulate foetal/neonatal innate immunity.

  • 47. Gbedande, K.
    et al.
    Ezinmegnon, S.
    Adeothy, A. -L
    Agbowai, C.
    Nouatin, O. P.
    Ibitokou, S.
    Borgella, S.
    Moutairou, K.
    Massougbodji, A.
    Varani, S.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Luty, A. J. F.
    Deloron, P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Fievet, N.
    Consequences of malaria during pregnancy on neonatal antigen presenting cell activation and on responses to toll-like receptors and P. falciparum antigens in Benin2011Inngår i: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 16, nr Special issue, supplement 1, s. 304-304Artikkel i tidsskrift (Fagfellevurdert)
  • 48. Gbedande, Komi
    et al.
    Cottrell, Gilles
    Vianou, Bertin
    Ibitokou, Samad
    Fernando, Aurax
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Salanti, Ali
    Moutairou, Kabirou
    Massougbodji, Achille
    Ndam, Nicaise Tuikue
    Deloron, Philippe
    Luty, Adrian J. F.
    Fievet, Nadine
    Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses2016Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 15, artikkel-id 485Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.

  • 49. Gbedande, Komi
    et al.
    Varani, Stefania
    Ibitokou, Samad
    Houngbegnon, Parfait
    Borgella, Sophie
    Nouatin, Odilon
    Ezinmegnon, Sem
    Adeothy, Adicatou-Iai
    Cottrell, Gilles
    Massougbodji, Achille
    Moutairou, Kabirou
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Deloron, Philippe
    Fievet, Nadine
    Luty, Adrian J. F.
    Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses2013Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 81, nr 8, s. 2686-2696Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protection from infections in early life relies extensively on innate immunity, but it is unknown whether and how maternal infections modulate infants' innate immune responses, thereby altering susceptibility to infections. Plasmodium falciparum causes pregnancy-associated malaria (PAM), and epidemiological studies have shown that PAM enhances infants' susceptibility to infection with P. falciparum. We investigated how PAM-mediated exposures in utero affect innate immune responses and their relationship with infection in infancy. In a prospective study of mothers and their babies in Benin, we investigated changes in Toll-like receptor (TLR)-mediated cytokine responses related to P. falciparum infections. Whole-blood samples from 134 infants at birth and at 3, 6, and 12 months of age were stimulated with agonists specific for TLR3, TLR4, TLR7/8, and TLR9. TLR-mediated interleukin 6 (IL-6) and IL-10 production was robust at birth and then stabilized, whereas tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) responses were weak at birth and then increased. In multivariate analyses, maternal P. falciparum infections at delivery were associated with significantly higher TLR3-mediated IL-6 and IL-10 responses in the first 3 months of life (P<0.05) and with significantly higher TLR3-, TLR7/8-, and TLR9-mediated TNF-alpha responses between 6 and 12 months of age (P<0.05). Prospective analyses showed that higher TLR3- and TLR7/8-mediated IL-10 responses at birth were associated with a significantly higher risk of P. falciparum infection in infancy (P<0.05). Neonatal and infant intracellular TLR-mediated cytokine responses are conditioned by in utero exposure through PAM late in pregnancy. Enhanced TLR-mediated IL-10 responses at birth are associated with an increased risk of P. falciparum infection, suggesting a compromised ability to combat infection in early life.

  • 50. Geels, Mark J
    et al.
    Imoukhuede, Egeruan B
    Imbault, Nathalie
    van Schooten, Harry
    McWade, Terry
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Dobbelaer, Roland
    Craig, Alister G
    Leroy, Odile
    European Vaccine Initiative: lessons from developing malaria vaccines2011Inngår i: Expert Review of Vaccines, ISSN 1476-0584, E-ISSN 1744-8395, Vol. 10, nr 12, s. 1697-1708Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against ?diseases of poverty? with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

123 1 - 50 of 134
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf