Journal article
IL-13 induced inflammation increases DPP4 abundance but does not enhance MERS-CoV replication in airway epithelia
The Journal of infectious diseases, Vol.229(5), pp.1419-1429
09/12/2023
DOI: 10.1093/infdis/jiad383
PMCID: PMC11095549
PMID: 37698016
Abstract
Background
Chronic pulmonary conditions such as asthma and COPD 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 IL-13, examining how this impacted DPP4 protein levels along with MERS-CoV entry and replication.
Results
IL-13 exposure for 3 days led to increased DPP4 protein abundance, while a 21-day treatment increased DPP4 levels and caused goblet cell metaplasia. Surprisingly, despite this increase in receptor availability, MERS-CoV entry and replication were not significantly impacted by IL-13 treatment.
Conclusions
Our results suggest that increased 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.
Details
- Title: Subtitle
- IL-13 induced inflammation increases DPP4 abundance but does not enhance MERS-CoV replication in airway epithelia
- Creators
- Kun Li - University of IowaJennifer A Bartlett - University of IowaChristine L Wohlford-Lenane - University of IowaBiyun Xue - University of IowaAndrew L Thurman - University of IowaThomas M Gallagher - Loyola University ChicagoAlejandro A Pezzulo - University of IowaPaul B McCray Jr - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of infectious diseases, Vol.229(5), pp.1419-1429
- DOI
- 10.1093/infdis/jiad383
- PMID
- 37698016
- PMCID
- PMC11095549
- NLM abbreviation
- J Infect Dis
- ISSN
- 0022-1899
- eISSN
- 1537-6613
- Publisher
- Oxford University Press (OUP)
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: P01 AI060699, R01 HL163024, K01 HL140261; name: University of Iowa Cells and Tissue Core; name: Center for Gene Therapy for Cystic Fibrosis, award: P30 DK054759; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation, award: PEZZUL20A1-KB; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust
- Language
- English
- Electronic publication date
- 09/12/2023
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984464516302771
Metrics
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