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Type I and III interferons disrupt lung epithelial repair during recovery from viral infection.
journal contributionposted on 2020-10-22, 11:08 authored by Jack Major, Stefania Crotta, Miriam Llorian, Teresa M McCabe, Hans Henrik Gad, Simon L Priestnall, Rune Hartmann, Andreas Wack
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).
Crick (Grant ID: 10206, Grant title: Wack FC001206)
Alveolar Epithelial CellsAnimalsApoptosisBronchoalveolar Lavage FluidCell DifferentiationCell ProliferationCells, CulturedCytokinesFemaleInfluenza A Virus, H3N2 SubtypeInterferon Type IInterferon-alphaInterferon-betaInterferonsLungMaleMiceOrthomyxoviridae InfectionsReceptor, Interferon alpha-betaReceptors, InterferonSignal TransductionTumor Suppressor Protein p53Wack FC001206BRF-ackFC-ackCBHPGeneral Science & Technology