Critical Roles for LIGHT and Its Receptors in Generating T Cell-Mediated Immunity during Leishmania donovani Infection

PLoS Pathogens

Geoff R. Hill¹  Carl Ware²  Stefanie Scheu³  Koji Tamada⁴  Fabian de Labastida Rivera⁵  Bernadette M. Saunders⁶  Michael J. Hickey⁶  Christian R. Engwerda⁷  Meru Sheel⁸  Fiona H. Amante⁸  Amanda C. Stanley⁸  Klaus Pfeffer⁸  Louise M. Randall⁸  Paul M. Kaye⁸  Patrick T. Bunn⁸  Ashraful Haque⁸  Yonghong Zhou⁸ 

[1] Centenary Institute, Newtown, New South Wales, Australia;Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia;Department of Pathobiology, School of Veterinary Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Infectious and Inflammatory Diseases Centre, Sanford

[2] Burnham Medical Research Institute, La Jolla, California, United States of America;Institute for Molecular Biology, University of Queensland, St Lucia, Queensland, Australia;Institute of Medical Microbiology and Hospital Hygiene, University of Duesseldorf, Duesseldorf, Germany;Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, Unites States of America;Queensland Institute of Medical Research and the Australian Centre for Vaccine Development, Herston, Queensland, Australia

关键词: Parasitic diseases;    T cells;    Leishmania donovani;    Spleen;    Protozoan infections;    Cytokines;    Granulomas;    Monocytes;   

DOI  :  10.1371/journal.ppat.1002279

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY