Differential Activation of NK Cells by Influenza A Pseudotype H5N1 and 1918 and 2009 Pandemic H1N1 Viruses
Differential Activation of NK Cells by Influenza A Pseudotype H5N1 and 1918 and 2009 Pandemic H1N1 Viruses
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DOI：
10.1128/jvi.00069-10
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发表时间：
2010-08-01
影响因子：
5.4
通讯作者：
Shu, Yuelong
中科院分区：
文献类型：
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作者：
Du, Ning;Zhou, Jianfang;Shu, Yuelong
自然杀伤 (NK) 细胞是先天免疫的效应细胞，在流感病毒感染后 48 小时被招募到肺部。病毒血凝素 (HA) 与细胞表面天然细胞毒性受体 NKp46 和 NKp44 之间的相互作用可以触发功能性 NK 细胞激活。最近，流感病毒的新亚型，例如H5N1和2009年大流行的H1N1，直接传播给人类，死亡率和发病率异常高。在这里，研究了人类 NK 细胞对这些病毒的反应。分别与 H5N1、1918 H1N1 和 2009 H1N1 假型颗粒 (pps) 相互作用后，观察到异质 NK 细胞的差异激活（CD69 和 CD107a 和γ干扰素 [IFN-γ] 产生上调以及 NKp46 下调），并且 CD56(dim) 子集的反应占主导地位。 H5N1 和 1918 H1N1 pps 触发的 NK 激活比 2009 H1N1 pps 触发的要强得多。 pps 与 NK 细胞的相互作用以及随后的内化部分是由 NKp46 介导的。 pps 的 NK 细胞激活表现出剂量依赖性，而病毒 HA 滴度的增加会减弱 NK 激活表型、细胞毒性和 IFN-γ 的产生。不同的宿主对不同流感病毒亚型或HA滴度的先天免疫反应可能与疾病的严重程度相关。
Natural killer (NK) cells are the effectors of innate immunity and are recruited into the lung 48 h after influenza virus infection. Functional NK cell activation can be triggered by the interaction between viral hemagglutinin (HA) and natural cytotoxicity receptors NKp46 and NKp44 on the cell surface. Recently, novel subtypes of influenza viruses, such as H5N1 and 2009 pandemic H1N1, transmitted directly to the human population, with unusual mortality and morbidity rates. Here, the human NK cell responses to these viruses were studied. Differential activation of heterogeneous NK cells (upregulation of CD69 and CD107a and gamma interferon [IFN-gamma] production as well as downregulation of NKp46) was observed following interactions with H5N1, 1918 H1N1, and 2009 H1N1 pseudotyped particles (pps), respectively, and the responses of the CD56(dim) subset predominated. Much stronger NK activation was triggered by H5N1 and 1918 H1N1 pps than by 2009 H1N1 pps. The interaction of pps with NK cells and subsequent internalization were mediated by NKp46 partially. The NK cell activation by pps showed a dosage-dependent manner, while an increasing viral HA titer attenuated NK activation phenotypes, cytotoxicity, and IFN-gamma production. The various host innate immune responses to different influenza virus subtypes or HA titers may be associated with disease severity.