A lack of Fas/FasL signalling leads to disturbances in the antiviral response during ectromelia virus infection

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• 作者：K. Bień ; Z. Sobańska ; J. Sokołowska ; P. Bąska ; Z. Nowak…
• 刊名：Archives of Virology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：161
• 期：4
• 页码：913-928
• 全文大小：2,136 KB
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• 作者单位：K. Bień (1)
  Z. Sobańska (2)
  J. Sokołowska (3)
  P. Bąska (4)
  Z. Nowak (5)
  A. Winnicka (6)
  M. Krzyzowska (1)
  
  1. Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland
  2. Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland
  3. Department of Morphological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland
  4. Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland
  5. Department of Genetics and Animal Breeding, Faculty of Animal Science, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland
  6. Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776, Warsaw, Poland
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Virology
  Medical Microbiology
  Infectious Diseases
  
• 出版者：Springer Wien
• ISSN：1432-8798

文摘

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.