Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
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DOI：
10.1073/pnas.1303275110
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发表时间：
2013-08-20
影响因子：
11.1
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
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作者：
Pang, Iris K.;Pillai, Padmini S.;Iwasaki, Akiko
促炎反应的诱导是宿主对入侵病原体的先天防御的标志。甲型流感病毒（IAV）感染的宿主识别依赖于模式识别受体，包括Toll样受体7（TLR 7）和视黄酸诱导基因-1（RIG-I），用于激活先天免疫应答。在这里，我们表明，生理低剂量的IAV感染后，病毒感测TLR 7或RIG-I诱导促炎程序，促进病毒复制。将感染野生型小鼠的支气管肺泡灌洗液转移到TLR 7和RIG-I途径缺陷小鼠的气道中足以恢复病毒复制效率。IAV感染的细胞的比较揭示了由TLR 7和RIG-I信号传导引起的炎症介质将病毒靶细胞募集到气道，从而增强呼吸道内的病毒载量。我们的数据表明，IAV利用生理水平的炎症反应来获得其复制优势，并突出了病毒与宿主先天免疫反应之间复杂的相互作用。
Induction of a proinflammatory response is the hallmark of host innate defense against invading pathogens. Host recognition of influenza A virus (IAV) infection relies on pattern-recognition receptors, including Toll-like receptor 7 (TLR7) and retinoic acid inducible gene-1 (RIG-I) for the activation of innate-immune responses. Here, we show that following a physiological low dose of IAV infection, viral sensing by either TLR7 or RIG-I induces a proinflammatory program that promotes viral replication. Transfer of bronchoalveolar lavage from infected wild-type mice into the airway of mice deficient in TLR7 and RIG-I pathways was sufficient to restore viral replication efficiency. Comparison of IAV-infected cells revealed that inflammatory mediators elicited by TLR7 and RIG-I signaling recruit viral target cells to the airway, thereby enhancing viral load within the respiratory tract. Our data suggest that IAV uses physiological levels of inflammatory responses for its replicative advantage and highlight the complex interplay between viruses and the host innate-immune responses.