Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13910-5. doi: 10.1073/pnas.1303275110. Epub 2013 Aug 5.
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.
诱导炎症反应是宿主先天防御入侵病原体的标志。宿主对甲型流感病毒 (IAV) 感染的识别依赖于模式识别受体，包括 Toll 样受体 7 (TLR7) 和视黄酸诱导基因-1 (RIG-I)，以激活先天免疫反应。在这里，我们表明，在生理低剂量的 IAV 感染后，TLR7 或 RIG-I 的病毒感应会诱导促进病毒复制的促炎程序。将来自感染野生型小鼠的支气管肺泡灌洗液转移到 TLR7 和 RIG-I 途径缺陷的小鼠的气道中足以恢复病毒复制效率。对 IAV 感染细胞的比较表明，TLR7 和 RIG-I 信号引发的炎症介质将病毒靶细胞募集到气道中，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复制优势，并强调了病毒与宿主先天免疫反应之间的复杂相互作用。
