Type I and III interferons disrupt lung epithelial repair during recovery from viral infection.
Science
; 369(6504): 712-717, 2020 08 07.
Article
in English
| MEDLINE | ID: covidwho-594812
ABSTRACT
Excessive cytokine signaling frequently exacerbates lung tissue damage during respiratory viral infection. Type I (IFN-α and IFN-ß) and III (IFN-λ) interferons are host-produced antiviral cytokines. Prolonged IFN-α and IFN-ß responses can lead to harmful proinflammatory effects, whereas IFN-λ 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-λ 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).
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interferon Type I
/
Cytokines
/
Interferons
/
Orthomyxoviridae Infections
/
Alveolar Epithelial Cells
/
Lung
Type of study:
Prognostic study
Language:
English
Journal:
Science
Year:
2020
Document Type:
Article
Affiliation country:
Science.abc2061
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