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

Citation

Fromm, PD and Kling, JC and Remke, A and Bogdan, C and Korner, H, Fatal leishmaniasis in the absence of TNF despite a strong Th1 response, Frontiers in Microbiology, 6, (January) Article 1520. ISSN 1664-302X (2016) [Refereed Article]


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Copyright 2016 the authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fmicb.2015.01520

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.

Item Details

Item Type:Refereed Article
Keywords:IFN-γ, T cell subtypes, cutaneous leishmaniasis, mouse models, tumor necrosis factor
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Kling, JC (Miss Jessica Kling)
Author:Remke, A (Ms Annika Remke)
Author:Korner, H (Professor Heinrich Korner)
ID Code:107818
Year Published:2016
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-03-24
Last Modified:2017-11-07
Downloads:50 View Download Statistics

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