Type III interferons disrupt the lung epithelial barrier upon viral recognition
Type III interferons disrupt the lung epithelial barrier upon viral recognition
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DOI：
10.1126/science.abc3545
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发表时间：
2020-08-07
期刊：
影响因子：
56.9
通讯作者：
Zanoni, Ivan
中科院分区：
文献类型：
--
作者：
Broggi, Achille;Ghosh, Sreya;Zanoni, Ivan
下呼吸道的病毒感染是死亡的主要原因。越来越多的证据表明，大多数严重病例的特点是免疫反应异常，不依赖于病毒负担。在这项研究中，我们评估了III型干扰素(干扰素-lambda)在RNA病毒诱导的发病机制中的作用。我们报告了干扰素-lambda存在于2019年冠状病毒病患者的下呼吸道，但不存在于上呼吸道(新冠肺炎)。在小鼠中，我们证明了由肺树突状细胞产生的干扰素-lambda对合成的病毒RNA的反应导致屏障损伤，导致对致死性细菌双重感染的易感性。这些发现为重新考虑干扰素-lambda的病理生理作用以及在临床实践中可能用于对抗地方性病毒，如流感病毒和新出现的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染提供了强有力的理由。
Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-lambda) contribute to the pathogenesis induced by RNA viruses. We report that IFN-lambda is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-lambda produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-lambda and its possible use in clinical practice against endemic viruses, such as influenza virus as well as the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.