Critical Roles for LIGHT and Its Receptors in Generating T Cell-Mediated Immunity during Leishmania donovani Infection
Year: 2011
Type: article
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.
Source: PLoS Pathogens
Authors: Amanda C. Stanley, Fabian de Labastida Rivera, Ashraful Haque, Meru Sheel, Yonghong Zhou, Fiona H. Amante, Patrick T. Bunn, Louise M. Randall, Klaus Pfeffer, Stefanie Scheu, Michael J. Hickey, Bernadette M. Saunders, Carl Ware, Geoff R. Hill, Koji Tamada, Paul M. Kaye, Christian R. Engwerda
Institutions: The University of Queensland, QIMR Berghofer Medical Research Institute, University of Pennsylvania, Heinrich Heine University Düsseldorf, Monash Medical Centre, Monash University, Centenary Institute, Sanford Burnham Prebys Medical Discovery Institute, University of Maryland, Baltimore, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, York University, University of York, Hull York Medical School
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
OpenAlex ID: W1984782555