Induction of natural killer cell responses by ectromelia virus controls infection
Induction of natural killer cell responses by ectromelia virus controls infection
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DOI：
10.1128/jvi.02061-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Buller, R. Mark L.
中科院分区：
文献类型：
--
作者：
Parker, April Keim;Parker, Scott;Buller, R. Mark L.
自然杀伤（NK）细胞在对病毒感染，特别是鼠巨细胞病毒（MCMV）和人疱疹病毒的先天免疫应答中发挥关键作用。在痘病毒感染中，NK细胞的作用不太清楚。我们通过抗体耗竭和遗传手段检测了去除NK细胞后C57 BL/6小鼠的疾病进展。我们发现，NK细胞是至关重要的生存和早期控制病毒复制在脾脏和在较小程度上在肝脏中的C57 BL/6小鼠。对各种基因敲除小鼠的研究表明，γ δ T细胞和NKT细胞在C57 BL/6小鼠痘模型中并不重要，并且在感染后6天，CD 4（+）和CD 8（+）T细胞不显示抗病毒活性，此时NK细胞的缺乏对脾和肝中的病毒滴度具有深远的影响。NK细胞的细胞毒性和/或γ干扰素（IFN-γ）分泌可能介导了控制靶器官中病毒感染所需的抗病毒作用。鼠痘病毒（ECTV）感染对NK细胞影响的研究表明，NK细胞在靶组织（脾脏和肝脏）内增殖，并在低剂量足垫感染后被激活，尽管激活机制似乎与MCMV观察到的配体依赖性激活不同。NK细胞IFN-γ分泌检测细胞内细胞因子染色瞬时在32至72小时后在淋巴结感染，这表明在建立一个Th 1反应的作用。这些结果证实了NK细胞在控制ECTV感染中的关键作用。
Natural killer (NK) cells play a pivotal role in the innate immune response to viral infections, particularly murine cytomegalovirus (MCMV) and human herpesviruses. In poxvirus infections, the role of NK cells is less clear. We examined disease progression in C57BL/6 mice after the removal of NK cells by both antibody depletion and genetic means. We found that NK cells were crucial for survival and the early control of virus replication in spleen and to a lesser extent in liver in C57BL/6 mice. Studies of various knockout mice suggested that gamma delta T cells and NKT cells are not important in the C57BL/6 mousepox model and CD4(+) and CD8(+) T cells do not exhibit antiviral activity at 6 days postinfection, when the absence of NK cells has a profound effect on virus titers in spleen and liver. NK cell cytotoxicity and/or gamma interferon (IFN-gamma) secretion likely mediated the antiviral effect needed to control virus infectivity in target organs. Studies of the effects of ectromelia virus (ECTV) infection on NK cells demonstrated that NK cells proliferate within target tissues (spleen and liver) and become activated following a low-dose footpad infection, although the mechanism of activation appears distinct from the ligand-dependent activation observed with MCMV. NK cell IFN-gamma secretion was detected by intracellular cytokine staining transiently at 32 to 72 h postinfection in the lymph node, suggesting a role in establishing a Th1 response. These results confirm a crucial role for NK cells in controlling an ECTV infection.