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

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    Author
    Stanley, AC; Rivera, FDL; Haque, A; Sheel, M; Zhou, Y; Amante, FH; Bunn, PT; Randall, LM; Pfeffer, K; Scheu, S; ...
    Date
    2011-10-01
    Source Title
    PLoS Pathogens
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Randall, Louise; Haque, Ashraful
    Affiliation
    Medicine and Radiology
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Stanley, A. C., Rivera, F. D. L., Haque, A., Sheel, M., Zhou, Y., Amante, F. H., Bunn, P. T., Randall, L. M., Pfeffer, K., Scheu, S., Hickey, M. J., Saunders, B. M., Ware, C., Hill, G. R., Tamada, K., Kaye, P. M. & Engwerda, C. R. (2011). Critical Roles for LIGHT and Its Receptors in Generating T Cell-Mediated Immunity during Leishmania donovani Infection. PLOS PATHOGENS, 7 (10), https://doi.org/10.1371/journal.ppat.1002279.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257143
    DOI
    10.1371/journal.ppat.1002279
    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.

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