1. Severity of neonatal influenza infection is driven by type I interferon and oxidative stress.
- Author
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Kumova OK, Galani IE, Rao A, Johnson H, Triantafyllia V, Matt SM, Pascasio J, Gaskill PJ, Andreakos E, Katsikis PD, and Carey AJ
- Subjects
- Animals, Mice, Antioxidants metabolism, Inflammation, Interferon-beta, Mice, Inbred C57BL, Animals, Newborn, Interferon Type I metabolism, Orthomyxoviridae Infections physiopathology, Oxidative Stress
- 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., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)
- Published
- 2022
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