107818 Journal Article.pdf (471.38 kB)
Fatal leishmaniasis in the absence of TNF despite a strong Th1 response
journal contribution
posted on 2023-05-18, 18:20 authored by Fromm, PD, Kling, JC, Remke, A, Bogdan, C, Heinrich KornerHeinrich KornerInduction 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.
History
Publication title
Frontiers in MicrobiologyVolume
6Issue
JanuaryArticle number
1520Number
1520Pagination
1-10ISSN
1664-302XDepartment/School
Menzies Institute for Medical ResearchPublisher
Frontiers Research FoundationPlace of publication
SwitzerlandRights statement
Copyright 2016 the authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/Repository Status
- Open