title: Role of Fas/FasL signaling in regulation of anti-viral response during HSV-2 vaginal infection in mice.
abstract: Fas receptor-Fas ligand (FasL) signaling is involved in apoptosis of virus-infected cells but increasing evidence accumulates on Fas receptor as a mediator of apoptosis-independent processes such as induction of activating and pro-inflammatory signals. In this study, we examined the role of Fas/FasL pathway in regulation of anti-viral response to genital HSV-2 infection using a murine model of HSV-2 infection applied to C57BL6/J, B6. MRL-Faslpr/J and B6Smn.C3-Faslgld/J mice. HSV-2 infection of Fas- and FasL-deficient mice led to decreased migration of IFN-γ expressing NK cells and CD4+ T cells, but not of γδ T cells, into the vaginal tissue. The vaginal tissues of HSV-2 infected Fas- and FasL-deficient mice showed increased production of IL-10, followed by low expression of the early CD69 activation marker on CD4+ and CD8+ T cells and increased numbers of regulatory T cells (Tregs). Experiments in co-cultures of CD4+ T cells and bone marrow derived dendritic cells showed that lack of bilateral Fas-FasL signaling led to expansion of Tregs and increased production of IL-10 and TGF-β1. Our results demonstrate that Fas/FasL can regulate development of tolerogenic dendritic cells and expansion of Tregs early during HSV-2 infection, which further influences effective anti-viral response.
authors.affiliation: Military Institute of Hygiene and Epidemiology, Warsaw, Poland; Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland. Electronic address: krzyzowskam@yahoo.com.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krzyzowska
authors.affiliation: Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Orłowski
authors.affiliation: Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bąska
authors.affiliation: Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Bodera
authors.affiliation: Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Zdanowski
authors.affiliation: Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Wanda
authors.initials: W
authors.lastname: Stankiewicz
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality; D018258:Herpesvirus 2, Human / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000821:virology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor
keywords: Dendritic cells; Fas/FasL; HSV-2; IL-10; Tregs