Bień K, Sobańska Z, Sokołowska J, Bąska P, Nowak Z, Winnicka A, Krzyzowska M
Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163, Warsaw, Poland.
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland.
Arch Virol. 2016 Apr;161(4):913-28. doi: 10.1007/s00705-015-2746-y. Epub 2016 Jan 18.
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.
痘苗病毒（ECTV）是一种正痘病毒（OPV），可引起鼠痘，相当于人类天花的鼠类疾病。Fas受体 - Fas配体（FasL）信号传导参与免疫细胞的凋亡和病毒特异性细胞毒性。Fas/FasL途径在ECTV感染期间控制局部炎症反应中也起着重要作用。在此，研究了Fas（-）（lpr）、FasL（-）（gld）和C57BL6野生型小鼠对ECTV莫斯科株的免疫反应。在ECTV-MOS感染期间，Fas和FasL小鼠的病毒滴度升高，自然杀伤细胞（NK细胞）、CD4（+）和CD8（+）T细胞总数减少，随后脾脏和淋巴结中表达IFN-γ的NK细胞、CD4（+）和CD8（+）T细胞百分比降低。在ECTV-MOS感染的第7天，与野生型小鼠相比，Fas和FasL缺陷小鼠脾脏和淋巴结中的调节性T细胞（Treg）计数最高。此外，在感染的第7天和第10天，我们观察到与野生型小鼠相比，Fas（-）和FasL（-）小鼠中表达PD-L1的树突状细胞数量明显更多。CD4（+）T细胞与骨髓来源的树突状细胞共培养实验表明，缺乏双侧Fas-FasL信号传导会导致Treg细胞扩增。总之，我们的结果表明，在ECTV感染期间，Fas/FasL可以调节耐受性树突状细胞和Treg的发育，导致免疫反应无效。
