Type III interferons disrupt the lung epithelial barrier upon viral recognition: Science

A. Broggi, S. Ghosh, B. Sposito, R. Spreafico, F. Balzarini, A. Lo Cascio, N. Clementi, M. de Santis, N. Mancini, F. Granucci, I. Zanoni

Research output: Contribution to journalArticlepeer-review

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-l) contribute to the pathogenesis induced by RNA viruses. We report that IFN-l is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-l 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-l 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. © 2020 American Association for the Advancement of Science. All rights reserved.
Original languageEnglish
Pages (from-to)706-712
Number of pages7
JournalSci.
Volume369
Issue number6504
DOIs
Publication statusPublished - 2020

Keywords

  • beta interferon
  • interferon
  • interferon induced helicase C domain containing protein 1
  • retinoic acid inducible protein I
  • toll like receptor 3
  • toll like receptor 7
  • type III interferon
  • unclassified drug
  • cytokine
  • interferon type III
  • polyinosinic polycytidylic acid
  • TLR3 protein, mouse
  • immune response
  • influenza
  • mortality
  • protein
  • RNA
  • severe acute respiratory syndrome
  • Article
  • cell proliferation
  • cell viability
  • coronavirus disease 2019
  • down regulation
  • host resistance
  • human
  • immunopathology
  • innate immunity
  • lung epithelium
  • lung lavage
  • Middle East respiratory syndrome coronavirus
  • nonhuman
  • pattern recognition
  • permeability barrier
  • priority journal
  • protein expression
  • signal transduction
  • throat culture
  • virus cell interaction
  • virus load
  • animal
  • Betacoronavirus
  • bronchoalveolar lavage fluid
  • C57BL mouse
  • Coronavirus infection
  • dendritic cell
  • immunology
  • lung
  • metabolism
  • mouse
  • nasopharynx
  • pandemic
  • pathology
  • physiology
  • respiratory mucosa
  • Staphylococcus infection
  • superinfection
  • virus pneumonia
  • Bacteria (microorganisms)
  • Coronavirus
  • Mus
  • Orthomyxoviridae
  • RNA viruses
  • SARS coronavirus
  • Animals
  • Bronchoalveolar Lavage Fluid
  • 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
  • Signal Transduction
  • Staphylococcal Infections
  • Superinfection
  • Toll-Like Receptor 3

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