Type III interferons disrupt the lung epithelial barrier upon viral recognition

被引：309

作者：

Broggi, Achille ^{[1
]}

Ghosh, Sreya ^{[1
]}

Sposito, Benedetta ^{[1
,2
]}

Spreafico, Roberto ^{[3
,9
]}

Balzarini, Fabio ^{[1
,2
]}

Lo Cascio, Antonino ^{[1
,2
]}

Clementi, Nicola ^{[4
]}

De Santis, Maria ^{[5
]}

Mancini, Nicasio ^{[4
,6
]}

Granucci, Francesca ^{[2
,7
]}

Zanoni, Ivan ^{[1
,2
,8
]}

机构：

[1] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Univ Milano Bicocca, Dept Biotechnol & Biosci, Milan, Italy

[3] Univ Calif Los Angeles, Inst Quantitat & Computat Biosci, Los Angeles, CA USA

[4] Univ Vita Salute San Raffaele, Lab Med Microbiol & Virol, Milan, Italy

[5] Humanitas Clin & Res Ctr IRCCS, Dept Rheumatol & Clin Immunol, Rozzano, Italy

[6] IRCCS San Raffaele Hosp, Milan, Italy

[7] Natl Inst Mol Genet INGM Romeo & Enrica Invernizz, Milan, Italy

[8] Harvard Med Sch, Boston Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[9] Vir Biotechnol, San Francisco, CA USA

来源：

SCIENCE | 2020年 / 369卷 / 6504期

关键词：

INFLUENZA; INFLAMMATION; PROTECTION; BACTERIA;

D O I：

10.1126/science.abc3545

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：706 / +

页数：36

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