Fatal Leishmaniasis in the absence of TNF despite a strong Th1 response

Fromm, Phillip D., Kling, Jessica C., Remke, Annika, Bogdan, Christian and Koerner, Heinrich (2016) Fatal Leishmaniasis in the absence of TNF despite a strong Th1 response. Frontiers in Microbiology, 6 JAN: 1520.1-1520.10. doi:10.3389/fmicb.2015.01520

Author Fromm, Phillip D.
Kling, Jessica C.
Remke, Annika
Bogdan, Christian
Koerner, Heinrich
Title Fatal Leishmaniasis in the absence of TNF despite a strong Th1 response
Journal name Frontiers in Microbiology   Check publisher's open access policy
ISSN 1664-302X
Publication date 2016-01-22
Year available 2016
Sub-type Article (original research)
DOI 10.3389/fmicb.2015.01520
Open Access Status DOI
Volume 6
Issue JAN
Start page 1520.1
End page 1520.10
Total pages 10
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Language eng
Formatted abstract
Induction of inducible nitric oxide synthase in mononuclear phagocytes by IFN-γ and innate tumor necrosis factor (TNF) provide the basis for an effective immune response to the intracellular parasite Leishmania (L.) major. In previous experiments, we observed a fatal visceral form of leishmaniasis in L. major-infected C57BL/6 TNF-/- mice. To further delineate the protective function of TNF and its receptor requirements, we comparatively assessed L. major-infected C57BL/6 mice that were either deficient for membrane and soluble TNF (Tnf-/-), for soluble TNF alone (memTnfΔ/Δ), or the TNF receptors type 1 (Tnfr1-/-) or type 2 (Tnfr2-/-). We detected locally and systemically increased levels of the cytokine IFN-γ in the absence of the TNF-TNFR1-signaling pathway. An analysis of transcription factors and cytokines revealed that activated Tnf-/- CD4+ T cells displayed a highly active Th1 phenotype with a strong usage of the T cell receptor Vβ5.1/2. From these data we conclude that the fatal outcome of L. major infection in Tnf-/- mice does not result from a skewed or deficient Th1 differentiation.
Keyword Cutaneous leishmaniasis
Tumor necrosis factor
T cell subtypes
Mouse models
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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UQ Diamantina Institute Publications
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