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

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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.

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Acknowledgments

This work was the subject of two Master Thesis projects (for KB and ZS) and was co-funded by grants from the Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences.

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Authors and Affiliations

  1. Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland

    K. Bień & M. Krzyzowska

  2. Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland

    Z. Sobańska

  3. Department of Morphological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776, Warsaw, Poland

    J. Sokołowska

  4. Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland

    P. Bąska

  5. Department of Genetics and Animal Breeding, Faculty of Animal Science, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786, Warsaw, Poland

    Z. Nowak

  6. Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776, Warsaw, Poland

    A. Winnicka

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  1. K. Bień
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Correspondence to M. Krzyzowska.

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Bień, K., Sobańska, Z., Sokołowska, J. et al. A lack of Fas/FasL signalling leads to disturbances in the antiviral response during ectromelia virus infection. Arch Virol 161, 913–928 (2016). https://doi.org/10.1007/s00705-015-2746-y

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  • DOI: https://doi.org/10.1007/s00705-015-2746-y

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