Journal article
IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo via eicosanoid signalling
EBioMedicine, Vol.120, 105920
10/2025
DOI: 10.1016/j.ebiom.2025.105920
PMCID: PMC12466150
PMID: 40957220
Abstract
Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signalling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents.
The role of the type 2 cytokine IL-13 on SARS-CoV-2 binding/entry, replication, and host response was investigated in primary HAE cells in vitro and in a model of mouse-adapted SARS-CoV-2 infection in vivo using single-cell and bulk RNA-sequencing approaches. Additionally, the responses were quantified using immunofluorescence, histopathology, immunohistochemistry and LC-MS/MS assays.
IL-13 protected airway epithelial cells from SARS-CoV-2 infection in vitro by decreasing the abundance of ACE2-expressing ciliated cells rather than by neutralisation in the airway surface liquid or by interferon-mediated antiviral effects. In contrast, IL-13 worsened disease severity in mice; the effects were mediated by eicosanoid signalling and were abolished in mice deficient in the phospholipase A
enzyme PLA2G2D.
IL-13-induced inflammation differentially affects multiple steps of COVID-19 pathogenesis. IL-13-induced inflammation may be protective against initial SARS-CoV-2 airway epithelial infection; however, it enhances disease progression in vivo. Blockade of IL-13 and/or eicosanoid signalling may be protective against progression to severe respiratory virus-induced lung diseases.
Carver Trust COVID-19 Grant; CF Foundation Iowa RDP; NIH 1R01HL163024; K01HL140261; NIH R01AI129269; NIH P01AI060699; NIH Grant P30 DK-54759; Cystic Fibrosis Foundation PEZZUL20A1-KB; Stead Family Foundation.
Details
- Title: Subtitle
- IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo via eicosanoid signalling
- Creators
- Shreya Ghimire - University of IowaBiyun Xue - University of IowaKun Li - University of IowaRyan M Gannon - University of IowaChristine L Wohlford-Lenane - University of IowaAndrew L Thurman - University of IowaHuiyu Gong - University of IowaGrace C Necker - University of IowaJian Zheng - University of IowaDavid K Meyerholz - University of IowaStanley Perlman - University of IowaPaul B McCray JrAlejandro A Pezzulo - University of Iowa
- Resource Type
- Journal article
- Publication Details
- EBioMedicine, Vol.120, 105920
- DOI
- 10.1016/j.ebiom.2025.105920
- PMID
- 40957220
- PMCID
- PMC12466150
- NLM abbreviation
- EBioMedicine
- ISSN
- 2352-3964
- eISSN
- 2352-3964
- Publisher
- ELSEVIER
- Grant note
- Carver Trust COVID-19 GrantCF Foundation Iowa RDPNIH: 1R01HL163024, K01HL140261, R01AI129269, P01AI060699, P30 DK-54759 Cystic Fibrosis Foundation: PEZZUL20A1-KB Stead Family Foundation
Carver Trust COVID-19 Grant; CF Foundation Iowa RDP; NIH 1R01HL163024; K01HL140261; NIH R01AI129269; NIH P01AI060699; NIH Grant P30 DK-54759; Cystic Fibrosis Foundation PEZZUL20A1-KB; Stead Family Foundation.
- Language
- English
- Electronic publication date
- 09/15/2025
- Date published
- 10/2025
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics); Internal Medicine
- Record Identifier
- 9984964237602771
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