Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2012 Aug 15;189(4):1843-9. doi: 10.4049/jimmunol.1200584. Epub 2012 Jul 13.
NK cells are critical for the innate immune control of poxviral infections. Previous studies have shown that NK cells are efficiently activated in response to infection with vaccinia virus (VV), the most studied member of the poxvirus family. However, it remains unknown whether the activation of NK cells in response to VV infection is tightly regulated. In this study, we showed that myeloid-derived suppressor cells (MDSCs) rapidly accumulated at the site of VV infection. In vivo depletion of MDSCs led to enhanced NK cell proliferation, activation, and function in response to VV infection. This was accompanied by an increase in mortality and systemic IFN-γ production. We further demonstrated that the granulocytic-MDSC (G-MDSC) subset was responsible for the suppression on NK cells and that this suppression was mediated by reactive oxygen species. These results indicate that G-MDSCs can negatively regulate NK cell activation and function in response to VV infection and suggest that manipulation of G-MDSCs could represent an attractive strategy for regulating NK cell activities for potential therapeutic benefits.
自然杀伤 (NK) 细胞对于痘病毒感染的固有免疫控制至关重要。先前的研究表明，NK 细胞在感染痘苗病毒 (VV) 时被有效激活，VV 是痘病毒家族中研究最多的成员。然而，目前尚不清楚 NK 细胞对 VV 感染的激活是否受到严格调控。在这项研究中，我们表明髓系来源的抑制细胞 (MDSC) 在 VV 感染部位迅速积累。体内耗尽 MDSC 会导致对 VV 感染的 NK 细胞增殖、激活和功能增强。这伴随着死亡率和全身 IFN-γ 产生的增加。我们进一步证明粒细胞 MDSC (G-MDSC) 亚群负责抑制 NK 细胞，这种抑制是由活性氧介导的。这些结果表明 G-MDSC 可以负向调节 NK 细胞对 VV 感染的激活和功能，并表明对 G-MDSC 的操纵可能代表一种有吸引力的策略，用于调节 NK 细胞的活性，以获得潜在的治疗益处。
