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. 1520. pp. 1-10.

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Induction of inducible nitric oxide synthase in mononuclear phagocytes by IFN-gamma 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(Delta/Delta)?), or the TNF receptors type 1 (Tnfr1(-/-)) or type 2 (Tnfr2(-/-)). We detected locally and systemically increased levels of the cytokine IFN-gamma 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 V beta 5.1/2. 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.

Item ID: 43342
Item Type: Article (Research - C1)
ISSN: 1664-302X
Keywords: cutaneous leishmaniasis, IFN-gamma, tumor necrosis factor, T cell subtypes, mouse models
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© 2016 Fromm, Kling, Remke, Bogdan and Körner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Date Deposited: 17 Feb 2016 07:31
FoR Codes: 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 60%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
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