A role for NKG2D in NK cell-mediated resistance to poxvirus disease.
A role for NKG2D in NK cell-mediated resistance to poxvirus disease.
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NKG2D在NK细胞介导的对痘病毒疾病的抗性中的作用。
DOI：
10.1371/journal.ppat.0040030
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发表时间：
2008-02-08
期刊：
影响因子：
6.7
通讯作者：
Sigal, Luis J.
中科院分区：
文献类型：
--
作者：
Fang, Min;Lanier, Lewis L.;Sigal, Luis J.
鼠痘病毒（ECTV）是一种引起鼠痘的正痘病毒（OPV），鼠痘相当于人类天花。C57 BL/6（B6）小鼠由于先天性和适应性免疫应答的协同作用而天然地对鼠痘具有抗性。先前的研究表明，自然杀伤（NK）细胞是先天免疫的一个组成部分，对B6小鼠抵抗鼠痘至关重要。然而，NK细胞介导的对OPV疾病的抗性的机制仍不明确。在这里，我们表明，B6小鼠对鼠痘的抵抗力需要NK细胞的直接溶细胞功能，以及它们增强T细胞反应的能力。此外，我们发现活化受体NKG 2D是最佳NK细胞介导的抗病性和致死性所必需的。总之，我们的研究结果对理解病原性病毒感染的自然抗性具有重要意义。鼠痘病毒（ECTV）引起鼠痘，一种相当于人类天花的鼠疾病。ECTV通常穿透外周，但通过淋巴系统迅速扩散到重要器官。在鼠痘敏感品系的小鼠中，ECTV感染的高潮是快速死亡或明显的鼠痘症状，这是由于病毒在重要器官，特别是肝脏中达到非常高的负荷。然而，一些品系的小鼠如C57 BL/6（B6）和129也感染ECTV，但通过控制重要器官中的病毒载量和清除病毒而没有疾病的临床症状，自然地抵抗鼠痘。自然杀伤（NK）细胞是先天免疫系统的细胞，以前显示在对鼠痘的自然抵抗中发挥重要作用。然而，NK细胞如何保护这种疾病仍然是未知的。在本文中，我们表明，NK细胞直接有助于抗病毒防御，抑制病毒传播到重要器官，也间接增加抗病毒T细胞反应。我们还证明，最佳的保护需要激活NK细胞受体NKG 2D，这有助于杀死ECTV感染的细胞。我们的工作对于理解病毒性疾病的自然抵抗力具有重要意义。
Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. C57BL/6 (B6) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses. Previous studies have shown that natural killer (NK) cells are a component of innate immunity that is essential for the B6 mice resistance to mousepox. However, the mechanism of NK cell–mediated resistance to OPV disease remains undefined. Here we show that B6 mice resistance to mousepox requires the direct cytolytic function of NK cells, as well as their ability to boost the T cell response. Furthermore, we show that the activating receptor NKG2D is required for optimal NK cell–mediated resistance to disease and lethality. Together, our results have important implication towards the understanding of natural resistance to pathogenic viral infections. Ectromelia virus (ECTV) causes mousepox, a murine disease that is the equivalent of human smallpox. ECTV normally penetrates through the periphery but rapidly spreads through the lymphatic system to vital organs. In mousepox-sensitive strains of mice, ECTV infection culminates with either rapid death or overt symptoms of mousepox due to very high loads that the virus reaches in vital organs, particularly the liver. However, some strains of mice such as C57BL/6 (B6) and 129 also become infected with ECTV but naturally resist mousepox by controlling the virus loads in vital organs and clearing the virus without clinical symptoms of disease. Natural killer (NK) cells are cells of the innate immune system previously shown to play an important role in natural resistance to mousepox. However, how NK cells protect from this disease is still unknown. In this paper we show that NK cells directly contribute to antiviral defenses by curbing virus dissemination to vital organs and also indirectly by augmenting the antiviral T cell response. We also demonstrate that optimal protection requires the activating NK cell receptor NKG2D which facilitates killing of ECTV-infected cells. Our work has important implications for the understanding of natural resistance to viral disease.
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