Archives of Virology

, Volume 161, Issue 4, pp 913–928 | Cite as

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

  • K. Bień
  • Z. Sobańska
  • J. Sokołowska
  • P. Bąska
  • Z. Nowak
  • A. Winnicka
  • M. Krzyzowska
Original Article

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.

Keywords

Dendritic Cell Natural Killer Cell West Nile Virus Antiviral Response FACSCalibur Flow Cytometer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this paper.

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • K. Bień
    • 1
  • Z. Sobańska
    • 2
  • J. Sokołowska
    • 3
  • P. Bąska
    • 4
  • Z. Nowak
    • 5
  • A. Winnicka
    • 6
  • M. Krzyzowska
    • 1
  1. 1.Department of Regenerative MedicineMilitary Institute of Hygiene and EpidemiologyWarsawPoland
  2. 2.Department of Molecular Genetics, Faculty of Biology and Environmental ProtectionUniversity of LodzLodzPoland
  3. 3.Department of Morphological Sciences, Faculty of Veterinary MedicineWarsaw University of Life SciencesWarsawPoland
  4. 4.Department of Preclinical Sciences, Faculty of Veterinary MedicineWarsaw University of Life SciencesWarsawPoland
  5. 5.Department of Genetics and Animal Breeding, Faculty of Animal ScienceWarsaw University of Life SciencesWarsawPoland
  6. 6.Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary MedicineWarsaw University of Life SciencesWarsawPoland

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