ReferencesLink to record
Permanent link

Direct link
An In Vitro Co-culture Mouse Model Demonstrates Efficient Vaccine-Mediated Control of Francisella tularensis SCHU S4 and Identifies Nitric Oxide as a Predictor of Efficacy
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
Show others and affiliations
2016 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 6, 152Article in journal (Refereed) Published
Abstract [en]

Francisella tularensis is a highly virulent intracellular bacterium and cell-mediated immunity is critical for protection, but mechanisms of protection against highly virulent variants, such as the prototypic strain F. tularensis strain SCHU S4, are poorly understood. To this end, we established a co-culture system, based on splenocytes from naive, or immunized mice and in vitro infected bone marrow-derived macrophages that allowed assessment of mechanisms controlling infection with F. tularensis. We utilized the system to understand why the clpB gene deletion mutant, Delta clpB, of SCHU S4 shows superior efficacy as a vaccine in the mouse model as compared to the existing human vaccine, the live vaccine strain (LVS). Compared to naive splenocytes, Delta clpB-, or LVS-immune splenocytes conferred very significant control of a SCHU S4 infection and the Delta clpB-immune splenocytes were superior to the LVS-immune splenocytes. Cultures with the Delta clpB-immune splenocytes also contained higher levels of IFN-gamma, IL-17, and GM-CSF and nitric oxide, and T cells expressing combinations of IFN-gamma, TNF-alpha, and IL-17, than did cultures with LVS-immune splenocytes. There was strong inverse correlation between bacterial replication and levels of nitrite, an end product of nitric oxide, and essentially no control was observed when BMDM from iNOS(-/-) mice were infected. Collectively, the co-culture model identified a critical role of nitric oxide for protection against a highly virulent strain of F. tularensis.

Place, publisher, year, edition, pages
2016. Vol. 6, 152
Keyword [en]
F. tularensis SCHU S4, in vitro co-culturemodel, mouse immune response, correlates of protection
National Category
Immunology Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-129814DOI: 10.3389/fcimb.2016.00152ISI: 000388557800001PubMedID: 27933275OAI: oai:DiVA.org:umu-129814DiVA: diva2:1063642
Available from: 2017-01-10 Created: 2017-01-09 Last updated: 2017-01-10Bibliographically approved

Open Access in DiVA

fulltext(2420 kB)2 downloads
File information
File name FULLTEXT01.pdfFile size 2420 kBChecksum SHA-512
e4b053ecfa8e392115388ecbae1e1e35b47ad494500c90c875d7b60e2e73b0f71cc50102df848d1e34155c383c8e803e52cbc5635a3c7f55739d1a89c6efb905
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Golovliov, IgorLindgren, HelenaEneslätt, KjellSjöstedt, Anders
By organisation
Molecular Infection Medicine Sweden (MIMS)Clinical Bacteriology
In the same journal
Frontiers in Cellular and Infection Microbiology
ImmunologyMicrobiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
Total: 2 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 51 hits
ReferencesLink to record
Permanent link

Direct link