Interleukin-22 Is Produced by Invariant Natural Killer T Lymphocytes during Influenza A Virus Infection POTENTIAL ROLE IN PROTECTION AGAINST LUNG EPITHELIAL DAMAGES
Interleukin-22 Is Produced by Invariant Natural Killer T Lymphocytes during Influenza A Virus Infection POTENTIAL ROLE IN PROTECTION AGAINST LUNG EPITHELIAL DAMAGES
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DOI：
10.1074/jbc.m111.304758
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发表时间：
2012-03-16
影响因子：
4.8
通讯作者：
Trottein, Francois
中科院分区：
文献类型：
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作者：
Paget, Christophe;Ivanov, Stoyan;Trottein, Francois
不变自然杀伤T细胞（iNKT）是一种非常规的脂质反应性α - β T淋巴细胞，在病毒感染期间的宿主反应中发挥关键作用，特别是通过快速产生细胞因子。它们在实验性甲型流感病毒（IAV）感染中的有益作用最近被提出，尽管所涉及的机制仍然难以捉摸。本研究表明，在体内IAV感染期间，小鼠肺部iNKT细胞产生ifn - γ和IL-22，这是一种与th17相关的细胞因子，对粘膜免疫至关重要。虽然允许病毒复制，但iNKT细胞产生IL-22不是由于这些细胞的IAV感染本身，而是由IAV感染的树突状细胞（dc）间接介导。我们发现，dc中病毒RNA传感器TLR7和rig - 1的激活对于触发iNKT细胞分泌IL-22很重要，而nod样受体NOD2和NLRP3则是必不可少的。不变的NKT细胞对受感染的dc提供的IL-1 β和IL-23作出反应，独立于CD1d分子释放IL-22。IL-22在体外保护iav感染的气道上皮细胞免于死亡，但对病毒复制没有作用。最后，在IAV感染早期，IL-22在控制肺上皮损伤中发挥积极作用。总体而言，IAV感染dc激活iNKT细胞，提供IL-22的快速来源，可能有利于保持肺上皮的完整性。
Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive alpha beta T lymphocytes that play a key role in host responses during viral infections, in particular through the swift production of cytokines. Their beneficial role during experimental influenza A virus (IAV) infection has recently been proposed, although the mechanisms involved remain elusive. Here we show that during in vivo IAV infection, mouse pulmonary iNKT cells produce IFN-gamma and IL-22, a Th17-related cytokine critical in mucosal immunity. Although permissive to viral replication, IL-22 production by iNKT cells is not due to IAV infection per se of these cells but is indirectly mediated by IAV-infected dendritic cells (DCs). We show that activation of the viral RNA sensors TLR7 and RIG-I in DCs is important for triggering IL-22 secretion by iNKT cells, whereas the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1 beta and IL-23 provided by infected DCs independently of the CD1d molecule to release IL-22. In vitro, IL-22 protects IAV-infected airway epithelial cells against mortality but has no role on viral replication. Finally, during early IAV infection, IL-22 plays a positive role in the control of lung epithelial damages. Overall, IAV infection of DCs activates iNKT cells, providing a rapid source of IL-22 that might be beneficial to preserve the lung epithelium integrity.