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.

Type III interferons disrupt the lung epithelial barrier upon viral recognition

De Santis, Maria;
2020

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.
Animals
Bronchoalveolar Lavage Fluid
COVID-19
Cell Proliferation
Coronavirus Infections
Cytokines
Dendritic Cells
Humans
Interferon Type I
Interferons
Lung
Mice
Mice, Inbred C57BL
Nasopharynx
Pandemics
Pneumonia, Viral
Poly I-C
Respiratory Mucosa
SARS-CoV-2
Signal Transduction
Staphylococcal Infections
Superinfection
Toll-Like Receptor 3
Betacoronavirus
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11699/68454
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