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- Title
The Type 2 Asthma Mediator IL-13 Inhibits Severe Acute Respiratory Syndrome Coronavirus 2 Infection of Bronchial Epithelium.
- Authors
Bonser, Luke R.; Eckalbar, Walter L.; Rodriguez, Lauren; Jiangshan Shen; Koh, Kyung Duk; Ghias, Khadija; Zlock, Lorna T.; Christenson, Stephanie; Woodruff, Prescott G.; Finkbeiner, Walter E.; Erle, David J.
- Abstract
Asthma is associated with chronic changes in the airway epithelium, a key target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many epithelial changes, including goblet cell metaplasia, are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. We found that IL-13 stimulation of differentiated human bronchial epithelial cells (HBECs) cultured at air–liquid interface reduced viral RNA recovered from SARS-CoV-2–infected cells and decreased double-stranded RNA, a marker of viral replication, to below the limit of detection in our assay. An intact mucus gel reduced SARS-CoV-2 infection of unstimulated cells, but neither a mucus gel nor SPDEF, which is required for goblet cell metaplasia, were required for the antiviral effects of IL-13. Bulk RNA sequencing revealed that IL-13 regulated 41 of 332 (12%) mRNAs encoding SARS-CoV-2–associated proteins that were detected in HBECs (.1.5-fold change; false discovery rate,0.05). Although both IL-13 and IFN-a each inhibit SARS-CoV-2 infection, their transcriptional effects differed markedly. Single-cell RNA sequencing revealed cell type–specific differences in SARS-CoV-2–associated gene expression and IL-13 responses. Many IL-13–induced gene expression changes were seen in airway epithelium from individuals with type 2 asthma and chronic obstructive pulmonary disease. IL-13 effects on airway epithelial cells may protect individuals with type 2 asthma from COVID-19 and could lead to identification of novel strategies for reducing SARS-CoV-2 infection.
- Subjects
COVID-19; SARS-CoV-2; BRONCHIAL spasm; LUNGS; CHRONIC obstructive pulmonary disease
- Publication
American Journal of Respiratory Cell & Molecular Biology, 2022, Vol 66, Issue 4, p391
- ISSN
1044-1549
- Publication type
Article
- DOI
10.1165/rcmb.2021-0364OC