The type 2 asthma mediator IL-13 inhibits SARS-CoV-2 infection of bronchial epithelium

Abstract Rationale Asthma is associated with chronic changes in the airway epithelium, a key target of SARS-CoV-2. Many epithelial changes are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. Objectives We sought to discover how IL-13 and other cytok...

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Bibliographic Details
Published in:bioRxiv 2021-02
Main Authors: Bonser, Luke R, Eckalbar, Walter L, Rodriguez, Lauren, Shen, Jiangshan, Kyung Duk Koh, Zlock, Lorna T, Christenson, Stephanie, Woodruff, Prescott G, Finkbeiner, Walter E, Erle, David J
Format: Article
Language:English
Subjects:
Asthma
Chronic infection
Chronic obstructive pulmonary disease
COVID-19
Cytokines
Double-stranded RNA
Epithelial cells
Epithelium
Gene expression
Infections
Interferon
Interleukin 13
Lung diseases
Obstructive lung disease
Respiratory tract
Severe acute respiratory syndrome coronavirus 2
Viral infections
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Summary:Abstract Rationale Asthma is associated with chronic changes in the airway epithelium, a key target of SARS-CoV-2. Many epithelial changes are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. Objectives We sought to discover how IL-13 and other cytokines affect expression of genes encoding SARS-CoV-2-associated host proteins in human bronchial epithelial cells (HBECs) and determine whether IL-13 stimulation alters susceptibility to SARS-CoV-2 infection. Methods We used bulk and single cell RNA-seq to identify cytokine-induced changes in SARS-CoV-2-associated gene expression in HBECs. We related these to gene expression changes in airway epithelium from individuals with mild-moderate asthma and chronic obstructive pulmonary disease (COPD). We analyzed effects of IL-13 on SARS-CoV-2 infection of HBECs. Measurements and Main Results Transcripts encoding 332 of 342 (97%) SARS-CoV-2-associated proteins were detected in HBECs (≥1 RPM in 50% samples). 41 (12%) of these mRNAs were regulated by IL-13 (>1.5-fold change, FDR < 0.05). Many IL-13-regulated SARS-CoV-2-associated genes were also altered in type 2 high asthma and COPD. IL-13 pretreatment reduced viral RNA recovered from SARS-CoV-2 infected cells and decreased dsRNA, a marker of viral replication, to below the limit of detection in our assay. Mucus also inhibited viral infection. Conclusions IL-13 markedly reduces susceptibility of HBECs to SARS-CoV-2 infection through mechanisms that likely differ from those activated by type I interferons. Our findings may help explain reports of relatively low prevalence of asthma in patients diagnosed with COVID-19 and could lead to new strategies for reducing SARS-CoV-2 infection. Competing Interest Statement The authors have declared no competing interest. Footnotes * Support: NIH awards U19 AI 077439 and R35 HL145235 (to DJE) and R00 HL135403 (to WLE), University of California, San Francisco Program for Breakthrough Biomedical Research (PBBR; to LRB).
DOI:10.1101/2021.02.25.432762