Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.

Autor:	Li K; Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA., Bartlett JA; Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA., Wohlford-Lenane CL; Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA., Xue B; Department of Internal Medicine, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA., Thurman AL; Department of Internal Medicine, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA., Gallagher TM; Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL., Pezzulo AA; Department of Internal Medicine, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA., McCray PB Jr; Department of Pediatrics, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA.; Department of Microbiology, Pappajohn Biomedical Institute, Carver College of Medicine, University of Iowa, Iowa City, IA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 May 15; Vol. 229 (5), pp. 1419-1429.
DOI:	10.1093/infdis/jiad383
Abstrakt:	Background: Chronic pulmonary conditions such as asthma and chronic obstructive pulmonary disease increase the risk of morbidity and mortality during infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). We hypothesized that individuals with such comorbidities are more susceptible to MERS-CoV infection due to increased expression of its receptor, dipeptidyl peptidase 4 (DPP4). Methods: We modeled chronic airway disease by treating primary human airway epithelia with the Th2 cytokine interleukin 13 (IL-13), examining how this affected DPP4 protein levels with MERS-CoV entry and replication. Results: IL-13 exposure for 3 days led to greater DPP4 protein abundance, while a 21-day treatment raised DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly affected by IL-13 treatment. Conclusions: Our results suggest that greater DPP4 abundance is likely not the primary mechanism leading to increased MERS severity in the setting of Th2 inflammation. Transcriptional profiling analysis highlighted the complexity of IL-13-induced changes in airway epithelia, including altered expression of genes involved in innate immunity, antiviral responses, and maintenance of the extracellular mucus barrier. These data suggest that additional factors likely interact with DPP4 abundance to determine MERS-CoV infection outcomes. Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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