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Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection.
- Source :
-
PLoS pathogens [PLoS Pathog] 2011 Oct; Vol. 7 (10), pp. e1002279. Date of Electronic Publication: 2011 Oct 06. - Publication Year :
- 2011
-
Abstract
- LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
Cell Proliferation drug effects
Dendritic Cells immunology
Dendritic Cells metabolism
Female
Interferon-gamma immunology
Interferon-gamma metabolism
Interleukin-12 biosynthesis
Interleukin-23 biosynthesis
Leishmania donovani immunology
Leishmaniasis, Visceral immunology
Leishmaniasis, Visceral parasitology
Liver parasitology
Liver pathology
Lymphotoxin beta Receptor immunology
Lymphotoxin beta Receptor metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Tumor Necrosis Factor, Member 14 immunology
Signal Transduction
T-Lymphocytes metabolism
Tumor Necrosis Factor Ligand Superfamily Member 14 genetics
Immunity, Cellular
Leishmania donovani pathogenicity
Leishmaniasis, Visceral pathology
Receptors, Tumor Necrosis Factor, Member 14 metabolism
T-Lymphocytes immunology
Tumor Necrosis Factor Ligand Superfamily Member 14 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 21998581
- Full Text :
- https://doi.org/10.1371/journal.ppat.1002279