DUOX2 regulates secreted factors in virus‐infected respiratory epithelial cells that contribute to neutrophil attraction and activation

The first line of defense against respiratory viruses relies on the antiviral and proinflammatory cytokine response initiated in infected respiratory epithelial cells. The cytokine response not only restricts virus replication and spreading, but also orchestrates the subsequent immune response. The...

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Published inThe FASEB journal Vol. 37; no. 2; pp. e22765 - n/a
Main Authors Kasumba, Dacquin M., Huot, Sandrine, Caron, Elise, Fortin, Audray, Laflamme, Cynthia, Zamorano Cuervo, Natalia, Lamontagne, Felix, Pouliot, Marc, Grandvaux, Nathalie
Format Journal Article
LanguageEnglish
Published United States 01.02.2023
Subjects
antiviral
Antiviral Agents - pharmacology
Chemokines - metabolism
cytokines
Cytokines - metabolism
Dual Oxidases - genetics
Dual Oxidases - metabolism
DUOX2
epithelial cells
Epithelial Cells - metabolism
Humans
inflammation
Neutrophils
redox
respiratory
virus
Viruses
inflammation
antiviral
epithelial cells
cytokines
respiratory
neutrophils
virus
DUOX2
redox
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Summary:The first line of defense against respiratory viruses relies on the antiviral and proinflammatory cytokine response initiated in infected respiratory epithelial cells. The cytokine response not only restricts virus replication and spreading, but also orchestrates the subsequent immune response. The epithelial Dual Oxidase 2 (DUOX2) has recently emerged as a regulator of the interferon antiviral response. Here, we investigated the role of DUOX2 in the inflammatory cytokine response using a model of A549 cells deficient in DUOX2 generated using Crispr‐Cas9 and infected by Sendai virus. We found that the absence of DUOX2 selectively reduced the induction of a restricted panel of 14 cytokines and chemokines secreted in response to Sendai virus by 20 to 89%. The secreted factors produced by epithelial cells upon virus infection promoted the migration, adhesion, and degranulation of primary human neutrophils, in part through the DUOX2‐dependent secretion of TNF and chemokines. In contrast, DUOX2 expression did not impact neutrophil viability or NETosis, thereby highlighting a selective impact of DUOX2 in neutrophil functions. Overall, this study unveils previously unrecognized roles of epithelial DUOX2 in the epithelial‐immune cells crosstalk during respiratory virus infection.
Bibliography:Marc Pouliot and Nathalie Grandvaux should be considered joint senior authors.
Dacquin M. Kasumba and Sandrine Huot should be considered joint first authors.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202201205R