Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response

Frontiers in Microbiology
Phillip D FrommHeinrich Körner

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 (memTnf(Δ/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.

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Citations

Jan 23, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katrin PaduchChristian Bogdan
Nov 22, 2019·Frontiers in Immunology·Niels-Arne MünckJan Ehrchen
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Roman FischerKlaus Pfizenmaier
Aug 8, 2020·Frontiers in Microbiology·Xinying LiXiaoying Liu
Oct 17, 2020·Cytokine·Imtissal Krayem, Marie Lipoldová

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Methods Mentioned

BETA
FACS
PMA
FCS
flow cytometry
PCR

Software Mentioned

Calc
FlowJo
REST
GraphPad Prism

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