Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2013 Jul 1;191(1):363-8. doi: 10.4049/jimmunol.1202714. Epub 2013 Jun 3.
NK cells play an important role in innate immune control of the infection with vaccinia virus (VV). However, it remains incompletely defined how the activation of NK cells in response to VV is regulated. In this study, we showed that STAT1 was critical for NK cell activation upon VV infection and the subsequent clearance of VV infection in vivo. We further demonstrated that STAT1 signaling in both NK and accessory cells such as dendritic cells was required for efficient NK cell activation upon VV infection. Mechanistically, STAT1 signaling in dendritic cells promoted the expression of NKG2D ligands, which is required for NK cell activation via the NKG2D pathway. Taken together, our data suggest that STAT1 mediates anti-VV effect by promoting NK cell activation through both NK-intrinsic and extrinsic mechanisms and may provide insights into the design of effective NK cell-based therapies for viral infections.
自然杀伤 (NK) 细胞在控制天花病毒 (VV) 感染的先天免疫中发挥着重要作用。然而，NK 细胞对 VV 的反应如何被激活仍不完全清楚。在这项研究中，我们表明 STAT1 对于 VV 感染后 NK 细胞的激活以及体内 VV 感染的清除至关重要。我们进一步证明，NK 细胞和辅助细胞（如树突状细胞）中的 STAT1 信号对于 VV 感染后 NK 细胞的有效激活是必需的。从机制上讲，树突状细胞中的 STAT1 信号促进了 NKG2D 配体的表达，这是通过 NKG2D 途径激活 NK 细胞所必需的。总之，我们的数据表明，STAT1 通过 NK 细胞内在和外在机制促进 NK 细胞激活来介导抗 VV 作用，这可能为设计有效的基于 NK 细胞的病毒感染治疗方法提供思路。
