Neonatal oxygen supplementation in mice leads to persistent modifications in NK cell functions during influenza A virus infection (INC8P.436)

Abstract

Abstract Supplemental oxygen is used to treat preterm infants in respiratory distress. However, this treatment can disrupt normal lung development and alter responses to respiratory insults. Similarly, exposure of newborn mice to 100% oxygen leads to alveolar simplification and altered host resistance to respiratory infection. Upon challenge with influenza A virus, adult mice exposed to neonatal hyperoxia exhibit higher morbidity and mortality, and survivors display hallmarks of pulmonary fibrosis, indicative of atypical repair. Natural Killer (NK) cells are key players in antiviral immunity; identifying and killing infected cells. Emerging evidence suggest they also help maintain homeostasis in peripheral tissues, including the lung, by promoting epithelial cell regeneration via IL-22. We tested the hypothesis that adult mice exposed to hyperoxia as neonates have modified NK cell responses to infection. We found that mice exposed to neonatal hyperoxia had fewer IL-22 producing pulmonary NK cells during influenza virus challenge, but an increase in IFN-γ producing NK cells. In reciprocal bone marrow chimera mice, diminished IL-22+ NK cells aligned with hyperoxia-exposed donors, irrespective of the host’s exposure status. Overall, our findings suggest that neonatal hyperoxia leads to long-term changes in the reparative versus cytotoxic nature of NK cells, due in part to intrinsic changes in hematopoietic cells. These differences may contribute to altered host responses to infection.