Differential role of TLR- and RLR-signaling in the immune responses to influenza a virus infection and vaccination
Differential role of TLR- and RLR-signaling in the immune responses to influenza a virus infection and vaccination
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DOI：
10.4049/jimmunol.179.7.4711
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Akira, Shizuo
中科院分区：
文献类型：
--
作者：
Koyama, Shohei;Ishii, Ken J.;Akira, Shizuo
先天免疫系统在体外以细胞类型特异性方式通过TLR 7或视黄酸诱导基因I识别甲型流感病毒，然而，体内抗病毒应答中MyD 88或干扰素β启动子刺激因子1（IPS-1）依赖性信号传导途径的生理功能仍不清楚。在这项研究中，我们表明，尽管MyD 88或IPS-1信号通路足以控制鼻内甲型流感病毒感染的初始抗病毒反应，但缺乏这两种通路的小鼠未能显示抗病毒反应，导致肺部病毒载量增加。相比之下，分别对显性血凝素或核蛋白Ags具有特异性的B细胞或CD 4 T细胞的诱导严格依赖于MyD 88信号传导，而不是IPS-1信号传导，而核蛋白Ag特异性CD 8 T细胞的诱导在不存在的情况下没有受损MyD 88或IPS-1。此外，用灭活病毒接种TLR 7和MyD 88缺陷型小鼠未能提供针对致死性活病毒攻击的保护。这些结果强烈表明，MyD 88或IPS-1信号通路足以用于初始抗病毒应答，而对甲型流感病毒的保护性适应性免疫应答由TLR 7-MyD 88通路控制。
The innate immune system recognizes influenza A virus via TLR 7 or retinoic acid-inducible gene I in a cell-type specific manner in vitro, however, physiological function(s) of the MyD88- or interferon-beta promoter stimulator 1 (IPS-1)-dependent signaling pathways in antiviral responses in vivo remain unclear. In this study, we show that although either MyD88- or IPS-1-signaling pathway was sufficient to control initial antiviral responses to intranasal influenza A virus infection, mice lacking both pathways failed to show antiviral responses, resulting in increased viral load in the lung. By contrast, induction of B cells or CD4 T cells specific to the dominant hemagglutinin or nuclear protein Ags respectively, was strictly dependent on MyD88 signaling, but not IPS-1 signaling, whereas induction of nuclear protein Ag-specific CD8 T cells was not impaired in the absence of either MyD88 or IPS-1. Moreover, vaccination of TLR7- and MyD88-deficient mice with inactivated virus failed to confer protection against a lethal live virus challenge. These results strongly suggest that either the MyD88 or IPS-1 signaling pathway is sufficient for initial antiviral responses, whereas the protective adaptive immune responses to influenza A virus are governed by the TLR7-MyD88 pathway.