title: Fas/FasL pathway participates in resolution of mucosal inflammatory response early during HSV-2 infection.
abstract: Apoptotic cell death is critical for maintaining integrity of the epithelia as well as for removal of the virus infected cells. We assessed the role of Fas/FasL-dependent pathway in apoptosis of genital epithelium during HSV-2 infection using a murine model of HSV-2 infection applied to C57BL6, MRL-Fas(lpr)/J (Fas-/-) and C3-Fasl(gld)/J (FasL-/-) mice and an in vitro model of HSV-2 infection in monocyte RAW 264.7 and keratinocyte 291.03C cell cultures and peritoneal macrophages. In contrast to keratinocyte in vitro cultures, HSV-2 infection of the monocytic cell cultures led to early induction of apoptosis. HSV-2 infection of peritoneal macrophages isolated from Fas- and FasL-deficient mice showed decreased activation of apoptosis, which could be further blocked by caspase-9 inhibitor. Infection of Fas and FasL-deficient mice increased the percentage of apoptotic cells and activation of caspase-9 in the vaginal tissue in comparison to C57BL6 wild type strain. Furthermore, Fas and FasL-deficient mice showed increased infiltration of neutrophiles in the vaginal mucosal epithelium at 3 and 7 day of infection in contrast to HSV-2 infected wild-type mice. Our results show that while the Fas/FasL pathway during HSV-2 infection of the vaginal epithelium plays an important role in controlling early local inflammatory response, mitochondrial apoptotic pathway also becomes activated by the inflammatory reaction.
authors.affiliation: Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland; Division of Immunology, 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.forename: Piotr
authors.initials: P
authors.lastname: Baska
authors.forename: Anna
authors.initials: A
authors.lastname: Grochowska
authors.forename: Piotr
authors.initials: P
authors.lastname: Orlowski
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Nowak
authors.forename: Anna
authors.initials: A
authors.lastname: Winnicka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D053453:Caspase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004848:Epithelium / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D053222:Fas Ligand Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006558:Herpes Genitalis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000821:virology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014621:Vagina / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019014:fas Receptor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D019014:fas Receptor; D053453:Caspase 9
keywords: Apoptosis; Caspase-9; Fas/FasL; HSV-2; ICP10; NETs; NK cells; ROS; STD; TNF; Vaginal epithelium; herpes simplex virus type 2; iNOS; inducible nitric oxide synthase; natural killer cells; neutrophil extracellular traps; reactive oxygen species; ribonucleotide reductase R1; sexually transmitted diseases; tumour necrosis factor