Abstract
Influenza virus (IV)-induced Type I Interferons Disrupt Alveolar Epithelial Barrier Function in the Developing Neonate
The Journal of immunology (1950), v 212(1_Supplement), 1141_5481
01 May 2024
Abstract
Abstract Type I interferons (IFN-I) limit IV replication in adults. However, IV-infected murine neonates lacking a functional IFN-I receptor (IFNAR-/-) have significantly improved survival and reduced lung pathology relative to wild-type (WT) neonates, indicating IFN-I toxicity in neonates. We hypothesized that IV-induced IFN-I signaling in type II alveolar epithelial cells (AT2s), the primary cell type of IV infection and initiator of host response, contribute to neonatal viral pathogenesis. Therefore, we performed RNA-Seq on AT2s purified from IV-infected IFNAR-/- and WT neonates at 1-, 2-, and 3-days post-infection (DPI). Pairwise comparisons highlighted differentially expressed genes (DEGs) dependent on genotype and timepoint, with DEGs highest between infected IFNAR-/- and WT neonates at 2 DPI and significant pathway upregulation of organ repair. Therefore, we hypothesized neonatal IV-infected IFNAR-/- AT2s possess improved barrier integrity early in infection. Indeed, genes associated with barrier dysfunction (il1b, tgfb1) increased in WT neonates over time, while tight junction gene cldn8 is higher in IFNAR-/- neonates. In addition, IF-stained IFNAR-/- lungs have improved expression of tight junction molecules, ZO-1 and occludin, in comparison to WT neonates at 6 DPI, a time of peak mortality. This suggests that early transcriptional differences in neonatal IFNAR-/- AT2s contribute to increased barrier integrity, mitigating later IV-induced damage and lung pathology.
Metrics
12 Record Views
Details
- Title
- Influenza virus (IV)-induced Type I Interferons Disrupt Alveolar Epithelial Barrier Function in the Developing Neonate
- Creators
- Abigail Onufer - Drexel UniversityJoshua Chang-Mell - Drexel UniversityLaura Cort - Drexel UniversityAbhishek Rao - Drexel UniversityNonto Mdluli - Drexel UniversityJudy Pascasio - Drexel UniversityAlison Carey - Drexel University
- Publication Details
- The Journal of immunology (1950), v 212(1_Supplement), 1141_5481
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- Microbiology and Immunology; Pediatrics
- Other Identifier
- 991021959241004721