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

A lack of Fas/FasL signalling leads to disturbances in the antiviral response during ectromelia... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

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

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Publisher
Springer Vienna
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2746-y
Publisher site
See Article on Publisher Site

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.

Journal

Archives of VirologySpringer Journals

Published: Apr 1, 2016

References

  • Ectromelia virus: the causative agent of mousepox
    Esteban, DJR; Buller, ML
  • Involvement of Fas and FasL in Ectromelia virus-induced apoptosis in mouse brain
    Krzyzowska, M; Cymerys, J; Winnicka, A; Niemiałtowski, M
  • Role of Fas/FasL signaling in regulation of anti-viral response during HSV-2 vaginal infection in mice
    Krzyzowska, M; Orłowski, P; Bąska, P; Bodera, P; Zdanowski, R; Stankiewicz, W
  • Natural killer cells in antiviral defense: function and regulation by innate cytokines
    Biron, A; Nguyen, KB; Pien, GC; Cousens, LP; Salazar-Mather, TP
  • Regulatory T cells: mechanisms of differentiation and function
    Josefowicz, SZ; Lu, LF; Rudensky, AY
  • CD40/CD40L signaling and its implication in health and disease
    Chatzigeorgiou, A; Lyberi, M; Chatzilymperis, G
  • Manipulating the PD-1 pathway to improve immunity
    Kamphorst, AO; Ahmed, R
  • B7–H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infection
    Wang, X; Zhang, Z; Zhang, S

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