Journal article
Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
Mucosal immunology, v 15(6), pp 1309-1320
Jun 2022
PMID: 36352099
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are antiviral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza virus (IV) model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24 h post IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population.
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Details
- Title
- Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
- Creators
- Ogan K Kumova - Drexel UniversityIoanna-Evdokia Galani - Biomedical Research Foundation of the Academy of AthensAbhishek Rao - Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USAHannah Johnson - Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USAVasiliki Triantafyllia - Biomedical Research Foundation of the Academy of AthensStephanie M Matt - Drexel UniversityJudy Pascasio - Pathology, Drexel University College of Medicine, Philadelphia, PA, USAPeter J Gaskill - Drexel UniversityEvangelos Andreakos - Biomedical Research Foundation of the Academy of AthensPeter D Katsikis - Erasmus MCAlison J Carey - Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA. ajc327@drexel.edu
- Publication Details
- Mucosal immunology, v 15(6), pp 1309-1320
- Publisher
- Springer Nature
- Grant note
- R21 DA049227 / NIDA NIH HHS K08 AI108791 / NIAID NIH HHS R01 DA039005 / NIDA NIH HHS R01 AI149801 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Pediatrics; College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:000882559100001
- Scopus ID
- 2-s2.0-85141625494
- Other Identifier
- 991020100212204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology