Effect of Neonatal Hyperoxia on Host Defense Children who were born prematurely and exposed to hyperoxia are more likely to have respiratory viral infections than children who were born at normal gestation and exposed to room air. Consistent with these epidemiologic findings, adult mice exposed to hyperoxia as newborns show increased susceptibility to influenza A virus infection as defined by impaired viral clearance, altered immune response, and fibrosis. Influenza A viral infection promotes fibrosis and a smooth muscle actin (red) in adult mice exposed to neonatal hyperoxia. While investigating how hyperoxia alters alveolar epithelial development, we identified a novel subpopulation of alveolar type II cells that selectively expresses genes that inhibit replication of viruses and bacteria, and control asymmetric cell division of stem/progenitor cells. Our laboratory is testing the hypothesis that hyperoxia permanently disrupts alveolar lung development by stimulating the differentiation of alveolar epithelial type II into type I cells and this is associated with enhanced susceptibility to influenza virus due to loss of a virus-resistant subpopulation of type II cells. In collaboration with other investigators, we also investigate whether impaired viral clearance in oxygen treated mice and children born prematurely is caused by disruption in the normal functions of CD8+ T cells. Selected References: O’Reilly MA, Yee M, Buczynski BW, Vitiello PF, Keng PC, Welle SL, Finkelstein JN, Dean DA, and Lawrence BP. Neonatal oxygen increases sensitivity to influenza A virus infection in adult mice by suppressing epithelial expression of Ear1. Am. J. Pathol. 181: 441-451, 2012. Giannandrea M, Yee M, O’Reilly MA, and Lawrence, BP. Memory CD8+ T cells are sufficient to alleviate impaired host resistance to influenza A virus infection caused by neonatal oxygen supplementation. Clinical and Vaccine Immunology. 19: 1432-1441, 2012. O'Reilly MA, Marr SH, Yee M, Mcgrath-Morrow SA, and Lawrence BP. Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus. Am J Respir Crit Care Med 177: 1103-1110, 2008.