CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis
CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis
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DOI：
10.1128/jvi.00550-16
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发表时间：
2016-07-01
影响因子：
5.4
通讯作者：
Lauzurica, Pilar
中科院分区：
文献类型：
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作者：
Notario, Laura;Alari-Pahissa, Elisenda;Lauzurica, Pilar
在宿主对病毒感染的反应过程中，跨膜 CD69 蛋白在所有免疫细胞中都高度上调。我们研究了 CD69 在小鼠对痘苗病毒 (VACV) 感染的免疫反应中的作用，并且我们报告说，CD69 的缺失增强了免疫功能正常和免疫缺陷小鼠感染后短期和长期对 VACV 的保护。自然杀伤 (NK) 细胞与感染控制的增强有关，因为当 NK 细胞耗尽时，差异会大大减小。 NK 细胞的这种作用并非基于 NK 细胞反应性的改变，因为 CD69 不会影响 NK 细胞响应主要组织相容性复合物 I 类 NK 细胞靶标或蛋白激酶 C 激活的激活阈值。相反，CD69 缺陷型感染小鼠的脾脏和腹膜中 NK 细胞数量增加。这不仅仅是CD69缺陷小鼠更好地控制感染的次要因素，因为未感染CD69(-/-)小鼠的脾脏和血液中的NK细胞数量已经增加。来自受感染小鼠的 CD69 缺陷型 NK 细胞的增殖能力没有改变。然而，CD69(-/-)淋巴细胞的自发细胞死亡率较低。因此，我们的结果表明，CD69 至少部分通过细胞稳态存活来限制对 VACV 感染的先天免疫反应。
During the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69(-/-) mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69(-/-) lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival.