HSV-2 regulates monocyte inflammatory response via the Fas/FasL pathway.
Monocytic cells represent important cellular elements of the innate and adaptive immune responses in viral infections. We assessed the role of Fas/FasL in promoting monocyte apoptosis during HSV-2 infection by using an in vitro model based on the murine RAW 264.7 monocytic cell line and an in vivo murine model of HSV-2 infection applied to C57BL6, MRL-Fas(lpr)/J (Fas-/-) and C3-Fasl(gld)/J (FasL-/-) mice. HSV-2 infection of the monocytic cell line led to early induction of apoptosis, with no protective expression of anti-apoptotic Bcl-2. HSV-2 infected monocytes up-regulated Fas and FasL expression early during in vitro infection but were susceptible to Fas induced apoptosis. The vaginal monocytes in the HSV-2 murine model of infection up-regulated FasL expression and were susceptible to Fas induced apoptosis. HSV-2 infection of Fas and FasL- deficient mice led to decreased apoptosis of monocytes and impaired recruitment of NK, CD4+ and CD8+ T cells within the infection sites. The vaginal lavages of HSV-2 infected Fas and FasL- deficient showed decreased production of CXCL9, CXCL10 and TNF-α in comparison to HSV-2 infected wild-type mice strain. The decreased recruitment of immune competent cells was accompanied by delayed virus clearance from the infected tissue. Triggering of the Fas receptor on HSV-2 infected monocytes in vitro up-regulated the expression of CXCL9 chemokines and the cytokine TNF-α. Our study provides novel insights on the role of Fas/FasL pathway not only in apoptosis of monocytes but also in regulating local immune response by monocytes during HSV-2 infection.
Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland. krzyzowskam@yahoo.com
Malgorzata
M
Krzyzowska
Piotr
P
Baska
Piotr
P
Orlowski
Robert
R
Zdanowski
Anna
A
Winnicka
Kristina
K
Eriksson
Wanda
W
Stankiewicz
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006558:Herpes Genitalis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014621:Vagina / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D053453:Caspase 9