title: Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection.
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.
authors: Queensland Institute of Medical Research and the Australian Centre for Vaccine Development, Herston, Queensland, Australia.
authors: Amanda C
authors: AC
authors: Stanley
authors: Fabian
authors: F
authors: de Labastida Rivera
authors: Ashraful
authors: A
authors: Haque
authors: Meru
authors: M
authors: Sheel
authors: Yonghong
authors: Y
authors: Zhou
authors: Fiona H
authors: FH
authors: Amante
authors: Patrick T
authors: PT
authors: Bunn
authors: Louise M
authors: LM
authors: Randall
authors: Klaus
authors: K
authors: Pfeffer
authors: Stefanie
authors: S
authors: Scheu
authors: Michael J
authors: MJ
authors: Hickey
authors: Bernadette M
authors: BM
authors: Saunders
authors: Carl
authors: C
authors: Ware
authors: Geoff R
authors: GR
authors: Hill
authors: Koji
authors: K
authors: Tamada
authors: Paul M
authors: PM
authors: Kaye
authors: Christian R
authors: CR
authors: Engwerda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008099:Liver / Q000469:parasitology / Q000473:pathology; D053259:Lymphotoxin beta Receptor / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D053759:Interleukin-23; D053259:Lymphotoxin beta Receptor; D053240:Receptors, Tumor Necrosis Factor, Member 14; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D018664:Interleukin-12; D007371:Interferon-gamma