Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Jack Major, The Francis Crick Institute
  • ,
  • Stefania Crotta, The Francis Crick Institute
  • ,
  • Miriam Llorian, The Francis Crick Institute
  • ,
  • Teresa M McCabe, The Francis Crick Institute
  • ,
  • Hans Henrik Gad
  • Simon L Priestnall, The Royal Veterinary College
  • ,
  • Rune Hartmann
  • Andreas Wack, The Francis Crick Institute

Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-α/β) and III (IFN-λ) interferons are host-produced antiviral cytokines. Prolonged IFN-α/β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, inducing localized antiviral immunity. Here we show that IFN signaling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity, and susceptibility to bacterial superinfections. Thus, excessive or prolonged IFN-production aggravates viral infection by impairing lung epithelial regeneration. Therefore, timing and duration are critical parameters of endogenous IFN action and should be considered carefully for IFN therapeutic strategies against viral infections like influenza and coronavirus disease 2019 (COVID-19).

Original languageEnglish
JournalScience (New York, N.Y.)
Volume369
Issue6504
Pages (from-to)712-717
ISSN0036-8075
DOIs
Publication statusPublished - Aug 2020

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