title: Fas/FasL pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs.
abstract: Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response.
authors: Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.
authors: Karolina
authors: K
authors: Bień
authors: Department of Morphological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland.
authors: Justyna
authors: J
authors: Sokołowska
authors: Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland.
authors: Piotr
authors: P
authors: Bąska
authors: Department of Genetics and Animal Breeding, Faculty of Animal Science, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland.
authors: Zuzanna
authors: Z
authors: Nowak
authors: Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.
authors: Wanda
authors: W
authors: Stankiewicz
authors: Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.
authors: Malgorzata
authors: M
authors: Krzyzowska
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004482:Ectromelia, Infectious / Q000276:immunology*; D053222:Fas Ligand Protein / Q000502:physiology*; D005260:Female; D007249:Inflammation / Q000209:etiology*; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor