Article ; Online: Type III interferons disrupt the lung epithelial barrier upon viral recognition.
2020 Volume 369, Issue 6504, Page(s) 706–712
Abstract: 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 ...
| Abstract | 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-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-λ 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-λ 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. |
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| MeSH term(s) | Animals ; Betacoronavirus ; Bronchoalveolar Lavage Fluid/immunology ; COVID-19 ; Cell Proliferation ; Coronavirus Infections/immunology ; Coronavirus Infections/metabolism ; Cytokines/metabolism ; Dendritic Cells/metabolism ; Humans ; Interferon Type I/metabolism ; Interferons/metabolism ; Interferons/physiology ; Lung/immunology ; Lung/metabolism ; Lung/pathology ; Mice ; Mice, Inbred C57BL ; Nasopharynx/immunology ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/metabolism ; Poly I-C/administration & dosage ; Respiratory Mucosa/pathology ; SARS-CoV-2 ; Signal Transduction ; Staphylococcal Infections/metabolism ; Superinfection ; Toll-Like Receptor 3/metabolism |
| Chemical Substances | Cytokines ; Interferon Type I ; TLR3 protein, mouse ; Toll-Like Receptor 3 ; interferon type III ; Interferons (9008-11-1) ; Poly I-C (O84C90HH2L) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-06-11 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 128410-1 |
| ISSN | 1095-9203 ; 0036-8075 |
| ISSN (online) | 1095-9203 |
| ISSN | 0036-8075 |
| DOI | 10.1126/science.abc3545 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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