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

TY - JOUR

T1 - Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

AU - Major, Jack

AU - Crotta, Stefania

AU - Llorian, Miriam

AU - McCabe, Teresa M

AU - Gad, Hans Henrik

AU - Priestnall, Simon L

AU - Hartmann, Rune

AU - Wack, Andreas

N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2020/8/7

Y1 - 2020/8/7

N2 - Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-a and IFN-b) and III (IFN-l) interferons are host-produced antiviral cytokines. Prolonged IFN-a and IFN-b responses can lead to harmful proinflammatory effects, whereas IFN-l mainly signals in epithelia, thereby inducing localized antiviral immunity. In this work, we show that IFN signaling interferes with lung repair during influenza recovery in mice, with IFN-l driving these effects most potently. IFN-induced protein p53 directly reduces epithelial proliferation and differentiation, which increases disease severity and susceptibility to bacterial superinfections. Thus, excessive or prolonged IFN production aggravates viral infection by impairing lung epithelial regeneration. Timing and duration are therefore critical parameters of endogenous IFN action and should be considered carefully for IFN therapeutic strategies against viral infections such as influenza and coronavirus disease 2019 (COVID-19).

AB - Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-a and IFN-b) and III (IFN-l) interferons are host-produced antiviral cytokines. Prolonged IFN-a and IFN-b responses can lead to harmful proinflammatory effects, whereas IFN-l mainly signals in epithelia, thereby inducing localized antiviral immunity. In this work, we show that IFN signaling interferes with lung repair during influenza recovery in mice, with IFN-l driving these effects most potently. IFN-induced protein p53 directly reduces epithelial proliferation and differentiation, which increases disease severity and susceptibility to bacterial superinfections. Thus, excessive or prolonged IFN production aggravates viral infection by impairing lung epithelial regeneration. Timing and duration are therefore critical parameters of endogenous IFN action and should be considered carefully for IFN therapeutic strategies against viral infections such as influenza and coronavirus disease 2019 (COVID-19).

UR - https://www.scopus.com/pages/publications/85087681982

U2 - 10.1126/science.abc2061

DO - 10.1126/science.abc2061

M3 - Journal article

C2 - 32527928

SN - 0036-8075

VL - 369

SP - 712

EP - 717

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6504

ER -