Both the Fas ligand and inducible nitric oxide synthase are needed for control of parasite replication within lesions in mice infected with Leishmania major whereas the contribution of tumor necrosis factor is minimal.

Details

Serval ID
serval:BIB_961D759FAFEA
Type
Article: article from journal or magazin.
Collection
Publications
Title
Both the Fas ligand and inducible nitric oxide synthase are needed for control of parasite replication within lesions in mice infected with Leishmania major whereas the contribution of tumor necrosis factor is minimal.
Journal
Infection and Immunity
Author(s)
Chakour R., Guler R., Bugnon M., Allenbach C., Garcia I., Mauël J., Louis J., Tacchini-Cottier F.
ISSN
0019-9567 (Print)
ISSN-L
0019-9567
Publication state
Published
Issued date
2003
Volume
71
Number
9
Pages
5287-5295
Language
english
Abstract
Following infection with the protozoan parasite Leishmania major, C57BL/6 mice develop a small lesion that heals spontaneously. Resistance to infection is associated with the development of CD4(+) Th1 cells producing gamma interferon (IFN-gamma) and tumor necrosis factor (TNF), which synergize in activating macrophages to their microbicidal state. We show here that C57BL/6 mice lacking both TNF and Fas ligand (FasL) (gld TNF(-/-) mice) infected with L. major neither resolved their lesions nor controlled Leishmania replication despite the development of a strong Th1 response. Comparable inducible nitric oxide synthase (iNOS) activities were detected in lesions of TNF(-/-), gld TNF(-/-), and gld mice, but only gld and gld TNF(-/-) mice failed to control parasite replication. Parasite numbers were high in gld mice and even more elevated in gld TNF(-/-) mice, suggesting that, in addition to iNOS, the Fas/FasL pathway is required for successful control of parasite replication and that TNF contributes only a small part to this process. Furthermore, FasL was shown to synergize with IFN-gamma for the induction of leishmanicidal activity within macrophages infected with L. major in vitro. Interestingly, TNF(-/-) mice maintained large lesion size throughout infection, despite being able to largely control parasite numbers. Thus, IFN-gamma, FasL, and iNOS appear to be essential for the complete control of parasite replication, while the contribution of TNF is more important in controlling inflammation at the site of parasite inoculation.
Keywords
Animals, Fas Ligand Protein, Interferon-gamma/metabolism, Leishmania major/growth & development, Leishmania major/immunology, Leishmaniasis/etiology, Leishmaniasis/immunology, Lymph Nodes/immunology, Macrophages/immunology, Macrophages/parasitology, Membrane Glycoproteins/deficiency, Membrane Glycoproteins/genetics, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Nitric Oxide/metabolism, Nitric Oxide Synthase/physiology, Nitric Oxide Synthase Type II, Th1 Cells/immunology, Tumor Necrosis Factor-alpha/deficiency, Tumor Necrosis Factor-alpha/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:08
Last modification date
20/08/2019 15:58
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