Type I and III interferons disrupt lung epithelial repair during recovery from viral infection
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Jack Major Stefania Crotta Miriam Llorian Sopena Teresa M McCabe Hans Henrik Gad Simon Priestnall Rune Hartmann Andreas WackAbstract
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).
Journal details
Journal
Science
Volume
369
Issue number
6504
Pages
712-717
Available online
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Full text links
Publisher website (DOI)
10.1126/science.abc2061
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Europe PubMed Central
32527928
Pubmed
32527928
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