tetano
Editor, Senior Moderator
Science
. 2020 Jun 11;eabc2061.
doi: 10.1126/science.abc2061. Online ahead of print.
Type I and III Interferons Disrupt Lung Epithelial Repair During Recovery From Viral Infection
Jack Major[SUP] 1 [/SUP], Stefania Crotta[SUP] 1 [/SUP], Miriam Llorian[SUP] 2 [/SUP], Teresa M McCabe[SUP] 1 [/SUP], Hans Henrik Gad[SUP] 3 [/SUP], Simon L Priestnall[SUP] 4 5 [/SUP], Rune Hartmann[SUP] 3 [/SUP], Andreas Wack[SUP] 6 [/SUP]
Affiliations
Abstract
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).
. 2020 Jun 11;eabc2061.
doi: 10.1126/science.abc2061. Online ahead of print.
Type I and III Interferons Disrupt Lung Epithelial Repair During Recovery From Viral Infection
Jack Major[SUP] 1 [/SUP], Stefania Crotta[SUP] 1 [/SUP], Miriam Llorian[SUP] 2 [/SUP], Teresa M McCabe[SUP] 1 [/SUP], Hans Henrik Gad[SUP] 3 [/SUP], Simon L Priestnall[SUP] 4 5 [/SUP], Rune Hartmann[SUP] 3 [/SUP], Andreas Wack[SUP] 6 [/SUP]
Affiliations
- PMID: 32527928
- DOI: 10.1126/science.abc2061
Abstract
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).