Respiratory Influenza Virus Infection Induces Memory-like Liver NK Cells in Mice
Respiratory Influenza Virus Infection Induces Memory-like Liver NK Cells in Mice
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呼吸道流感病毒感染诱导小鼠肝脏产生记忆样 NK 细胞
DOI：
10.4049/jimmunol.1502186
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发表时间：
2017-02-01
影响因子：
4.4
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
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作者：
Li, Tingting;Wang, Jian;Tian, Zhigang
虽然NK细胞被归类为先天免疫细胞，但最近的研究表明，NK细胞转化为长寿命记忆细胞，在某些小鼠模型中有助于二次免疫反应。然而，NK细胞是否对急性流感病毒感染产生ag特异性记忆反应尚未被研究。在这里，我们表明，与先前的研究一致，肺NK细胞在原发性流感病毒感染后的病毒增殖控制中发挥重要作用。然而，尽管肺NK细胞在感染后期表现出记忆表型，但这些细胞不能保护小鼠免受继发性流感病毒感染。有趣的是，来自流感病毒感染小鼠的肝脏NK细胞具有记忆表型，并保护小鼠免受继发性流感病毒感染。记忆样肝NK细胞表现为CD49a+DX5−表型，纯化后的肝CD49a+DX5−NK细胞过继转移到幼稚小鼠体内，然后进行病毒感染，结果产生保护性免疫并降低病毒滴度。此外，我们证明了原代灭活流感病毒诱导存在于Rag1−/−小鼠肝脏中的记忆NK细胞。总的来说，这些数据表明肝脏CD49a+DX5−NK细胞在初次感染后记住了流感病毒的Ag，并且在随后的感染中具有更强的保护作用。
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection. However, although lung NK cells display a memory phenotype at the late stage of infection, these cells do not protect mice against secondary influenza virus infection. Interestingly, liver NK cells from influenza virus–infected mice possess a memory phenotype and protect mice against secondary influenza virus infection. Memory-like liver NK cells display a CD49a+DX5− phenotype, and the adoptive transfer of purified liver CD49a+DX5− NK cells into naive mice followed by viral infection results in protective immunity and decreased viral titer. Moreover, we demonstrate that primary inactivated influenza virus induces memory NK cells residing in the liver of Rag1−/− mice. Collectively, these data suggest that liver CD49a+DX5− NK cells remember encountered Ag from influenza virus after primary infection and are more protective upon subsequent infection.