The Type 2 Asthma Mediator IL-13 Inhibits Severe Acute Respiratory Syndrome Coronavirus 2 Infection of Bronchial Epithelium

作者：Luke R. Bonser, Walter L. Eckalbar, Lauren Rodriguez, Jiangshan Jane Shen, Kyung Duk Koh, Khadija Ghias, Lorna Zlock, Stephanie A. Christenson, Prescott G. Woodruff, Walter E. Finkbeiner, David J. Erle · 发表于：American Journal of Respiratory Cell and Molecular Biology · 年份：2022 · DOI：10.1165/rcmb.2021-0364oc · 被引用次数：54 · 研究领域：Asthma and respiratory diseases、Respiratory viral infections research、Immune Cell Function and Interaction

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-α 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 fr...