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Changes in the levels of cytokines, chemokines and malaria specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut. University of Bamako, Mali.
Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
Vise andre og tillknytning
2012 (engelsk)Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 11, s. 109-Artikkel i tidsskrift (Fagfellevurdert) Published
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.

sted, utgiver, år, opplag, sider
2012. Vol. 11, s. 109-
Emneord [en]
cytokines, chemokines, antibodies, Plasmodium falciparum, Fulani, Dogon
HSV kategori
Forskningsprogram
immunologi
Identifikatorer
URN: urn:nbn:se:su:diva-80750DOI: 10.1186/1475-2875-11-109ISI: 000304761300001OAI: oai:DiVA.org:su-80750DiVA, id: diva2:557956
Merknad

AuthorCount:9;

Tilgjengelig fra: 2012-10-01 Laget: 2012-09-27 Sist oppdatert: 2017-12-07bibliografisk kontrollert
Inngår i avhandling
1. Malaria during pregnancy and childhood: A focus on soluble mediators and neutrophils
Åpne denne publikasjonen i ny fane eller vindu >>Malaria during pregnancy and childhood: A focus on soluble mediators and neutrophils
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

In areas where malaria is endemic, pregnant women and children bear the main burden of severe and life-threatening malarial disease. The aim of this work was to study the impact of Plasmodium falciparum infection on inflammatory responses in pregnant women and children residing in African countries. In paper I we investigated peripheral blood samples from pregnant women, living in Tanzania, for potential biomarkers of P. falciparum infection during pregnancy. We found that IL-10 and IP-10 were potential candidates, which increased upon infection, irrespective of gestational age. In addition, increased IL-10 and IP-10 and decreased RANTES levels were predictive of an infection. In paper II we investigated frequencies of peripheral blood-cell types and biomarkers upon infection, in pregnant women living in Benin, and assessed the predictive values of variables measured at inclusion for pregnancy outcomes at delivery. Higher IL-10 levels distinguished quantitative PCR-detectable, sub-microscopic infections, at inclusion, but not at delivery. Maternal anaemia at delivery was associated with increased numbers of circulating monocytes, Treg cells and IL-10 levels measured at inclusion. In paper III we investigated neutrophil functions in the context of pregnancy malaria in vivo and in vitro. Numbers of circulating neutrophils and IL-8 levels were reduced in the infected women, whilst increased levels of IL-8 were found in placental blood of those infected. In vitro assays suggested migration of neutrophils to infected placentas, which also was supported by histological examinations showing the presence of neutrophils containing hemozoin (Hz), in the infected placenta. Stimulation of neutrophils with various Hz preparations revealed distinct patterns of neutrophil activation. In paper IV we investigated cytokines and malaria-specific antibody titres in children belonging to two African ethnic groups, living in Mali, with known different susceptibility to malaria. The Fulani showed increased cytokines (IL-6, IL-8, IL-12, IFN-α, IFN-γ) and higher titres of malaria-specific antibody subclasses (IgG, IgM and IgG1-IgG3), compared to the Dogon. Taken together, this thesis shows that host biomarkers in peripheral blood may represent useful diagnostic markers for malaria during pregnancy. The neutrophil population was shown to be highly affected by the presence of P. falciparum parasites, suggesting a role for neutrophils during malaria infections. The Fulani, showed increased pro-inflammatory and antibody responses against P. falciparum parasites, as compared to Dogon, and these differences are established already at an early age.  

sted, utgiver, år, opplag, sider
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. s. 89
Emneord
Plasmodium falciparum, pregnancy, childhood, neutrophils, biomarkers, cytokines, chemokines, antibodies, Fulani, Dogon
HSV kategori
Forskningsprogram
immunologi
Identifikatorer
urn:nbn:se:su:diva-99916 (URN)978-91-7447-851-8 (ISBN)
Disputas
2014-03-21, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (engelsk)
Opponent
Veileder
Merknad

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.

Tilgjengelig fra: 2014-02-27 Laget: 2014-01-20 Sist oppdatert: 2014-02-17bibliografisk kontrollert

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