Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response
Induction of inducible nitric oxide synthase (iNOS) 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. We previously observed a fatal visceral form of leishmaniasis in L. ma...
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doaj-569c791b540e4a30b1684766d3356d2f2020-11-24T21:32:08ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-01-01610.3389/fmicb.2015.01520173151Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 ResponsePhillip D Fromm0Jessica eKling1Annika eRemke2Christian eBogdan3Heinrich eKorner4ANZAC Research InstituteMenzies Institute for Medical Research TasmaniaMenzies Institute for Medical Research TasmaniaUniversitaet ErlangenMenzies Institute for Medical Research TasmaniaInduction of inducible nitric oxide synthase (iNOS) 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. We previously 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∆/∆), 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-signalling 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01520/fullcutaneous leishmaniasisTumor necrosis factormouse modelsIFN-γT cells subpopulations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Phillip D Fromm Jessica eKling Annika eRemke Christian eBogdan Heinrich eKorner |
spellingShingle |
Phillip D Fromm Jessica eKling Annika eRemke Christian eBogdan Heinrich eKorner Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response Frontiers in Microbiology cutaneous leishmaniasis Tumor necrosis factor mouse models IFN-γ T cells subpopulations |
author_facet |
Phillip D Fromm Jessica eKling Annika eRemke Christian eBogdan Heinrich eKorner |
author_sort |
Phillip D Fromm |
title |
Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response |
title_short |
Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response |
title_full |
Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response |
title_fullStr |
Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response |
title_full_unstemmed |
Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response |
title_sort |
fatal leishmaniasis in the absence of tnf despite a strong th1 response |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2016-01-01 |
description |
Induction of inducible nitric oxide synthase (iNOS) 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. We previously 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∆/∆), 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-signalling 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. |
topic |
cutaneous leishmaniasis Tumor necrosis factor mouse models IFN-γ T cells subpopulations |
url |
http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01520/full |
work_keys_str_mv |
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