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Journal article
Influenza virus-induced type I interferons disrupt alveolar epithelial repair and tight junction integrity in the developing lung
Mucosal immunology, v 18(3), pp 607-619
19 Feb 2025
PMID: 39984053
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recently, we demonstrated that influenza A virus (IAV)-infected murine neonates lacking a functional IFN-I receptor (IFNAR
) had significantly improved survival and reduced lung pathology relative to wild-type (WT) neonates. In direct contrast, adult IFNAR
mice display enhanced morbidity following IAV infection relative to WT adults. We hypothesized that IAV-induced IFN-I signaling in primary neonatal type II alveolar epithelial cells (TIIECs), the main cell type of IAV infection and initiator of host response in the lung, contributed to age-specific viral pathogenesis. Multifactorial transcriptional analysis of purified TIIECs revealed age, not infection status, as the primary driver of transcriptional differences in TIIECs. Subsequent pathway analysis demonstrated IAV-infected IFNAR
neonates significantly upregulated cell proliferation, tissue repair and tight junction genes at 2-days post-infection (dpi), compared to WT neonates. Next, to determine if these growth and repair differences persisted later in infection, targeted analysis of repair gene expression and immunofluorescent quantification of pulmonary sealing tight junction molecules ZO-1 and occludin was performed at 6-dpi. Relative to WT neonates, IFNAR
neonates had significantly higher whole lung occludin staining and repair gene expression. Together, our data demonstrates IFN-I signaling is extremely pathogenic in the developing lung by disrupting alveolar repair and pulmonary barrier integrity.
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Details
- Title
- Influenza virus-induced type I interferons disrupt alveolar epithelial repair and tight junction integrity in the developing lung
- Creators
- Abigail P Onufer - Drexel UniversityJoshua Chang Mell - Drexel UniversityLaura Cort - Drexel UniversityAbhishek Rao - Drexel UniversityNontokozo V Mdluli - Drexel UniversityAlison J Carey - Drexel University
- Publication Details
- Mucosal immunology, v 18(3), pp 607-619
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- National Institutes of Health: R01AI149801 Hartwell Foundation Individual Biomedical Research Award
The authors thank Azad Ahmed and Bhaswati Sen at the Drexel University College of Medicine Genomics Core Facility for nucleic acid sequencing services. This work was supported by the National Institutes of Health (R01AI149801) to AJC, and The Hartwell Foundation Individual Biomedical Research Awards to JCM (2020) and AJC (2018) .
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Pediatrics
- Web of Science ID
- WOS:001510955300001
- Scopus ID
- 2-s2.0-85219068376
- Other Identifier
- 991022029670804721
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- Web of Science research areas
- Immunology