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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Springer Vienna
Copyright © 2016 by Springer-Verlag Wien
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
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    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
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  • Manipulating the PD-1 pathway to improve immunity
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