title: A lack of Fas/FasL signalling leads to disturbances in the antiviral response during ectromelia virus infection.
abstract: Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. Fas receptor-Fas ligand (FasL) signaling is involved in apoptosis of immune cells and virus-specific cytotoxicity. The Fas/FasL pathway also plays an important role in controlling the local inflammatory response during ECTV infection. Here, the immune response to the ECTV Moscow strain was examined in Fas (-) (lpr), FasL (-) (gld) and C57BL6 wild-type mice. During ECTV-MOS infection, Fas- and FasL mice showed increased viral titers, decreased total numbers of NK cells, CD4(+) and CD8(+) T cells followed by decreased percentages of IFN-γ expressing NK cells, CD4(+) and CD8(+) T cells in spleens and lymph nodes. At day 7 of ECTV-MOS infection, Fas- and FasL-deficient mice had the highest regulatory T cell (Treg) counts in spleen and lymph nodes in contrast to wild-type mice. Furthermore, at days 7 and 10 of the infection, we observed significantly higher numbers of PD-L1-expressing dendritic cells in Fas (-) and FasL (-) mice in comparison to wild-type mice. Experiments in co-cultures of CD4(+) T cells and bone-marrow-derived dendritic cells showed that the lack of bilateral Fas-FasL signalling led to expansion of Tregs. In conclusion, our results demonstrate that during ECTV infection, Fas/FasL can regulate development of tolerogenic DCs and Tregs, leading to an ineffective immune response.
authors.affiliation: Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bień
authors.affiliation: Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Sobańska
authors.affiliation: Department of Morphological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Sokołowska
authors.affiliation: Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Bąska
authors.affiliation: Department of Genetics and Animal Breeding, Faculty of Animal Science, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Nowak
authors.affiliation: Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Winnicka
authors.affiliation: Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland. krzyzowskam@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Krzyzowska
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology; D002460:Cell Line; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000502:physiology / Q000821:virology; D004481:Ectromelia virus; D004482:Ectromelia, Infectious / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007694:Killer Cells, Natural; D008198:Lymph Nodes; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013154:Spleen; D013997:Time Factors; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor