IFN-γ increases susceptibility to influenza A infection through suppression of group II innate lymphoid cells.
IFN-γ increases susceptibility to influenza A infection through suppression of group II innate lymphoid cells.
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DOI：
10.1038/mi.2017.41
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发表时间：
2018-01
影响因子：
8
通讯作者：
Metzger DW
中科院分区：
文献类型：
--
作者：
Califano D;Furuya Y;Roberts S;Avram D;McKenzie ANJ;Metzger DW
在流感病毒感染后，呼吸道中经常观察到干扰素-γ水平升高，但其潜在作用尚不清楚。我们现在证明，流感诱导的干扰素-γ在受到大流行H1N1 A/CA/04/2009流感病毒的攻击后，限制了肺内天然淋巴细胞组II(ILC2)的保护性功能。具体地说，干扰素-γ缺乏导致ILC2活性增强，其特征是IL-5和两用调节素的产生增加，组织完整性改善，但ILC2数量、病毒载量或清除没有变化。我们进一步发现，干扰素-γ缺陷小鼠以及中和抗干扰素-γ抗体处理的野生型动物，对H1N1 A/CA/04/2009流感病毒的致死性感染的易感性降低，而且生存依赖于IL-5的存在。在ILC2缺陷的动物中未观察到干扰素-γ中和的有益效果。这些数据支持新的概念，即干扰素-γ可以通过限制ILC2的活性在流感的发病机制中发挥有害作用。因此，ILC2活性的调节是流感感染后治疗的潜在靶点。
Increased levels of IFN-γ are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-γ restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 influenza virus. Specifically, IFN-γ deficiency resulted in enhanced ILC2 activity, characterized by increased production of IL-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance. We further found that IFN-γ-deficient mice, as well as wild-type animals treated with neutralizing anti-IFN-γ antibody, exhibited decreased susceptibility to lethal infection with H1N1 A/CA/04/2009 influenza virus, and moreover that survival was dependent on the presence of IL-5. The beneficial effects of IFN-γ neutralization were not observed in ILC2-deficient animals. These data support the novel concept that IFN-γ can play a detrimental role in the pathogenesis of influenza through a restriction in ILC2 activity. Thus, regulation of ILC2 activity is a potential target for post-infection therapy of influenza.
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影响因子：
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DOI：
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发表时间：
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期刊：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
Metzger DW