Abstract
Ultrafine particles (UFPs, ≤ 100 nm diameter) are a class of particulate matter pollutants ubiquitous in urban environments but generally lack explicit regulatory standards. Findings from our mouse model employing UFP exposure during pregnancy demonstrate offspring sex-specific effects on pulmonary immune responses when neonates are challenged with respiratory syncytial virus (RSV), a frequent cause of infant respiratory infection and hospitalization. We show that a lack of Nrf2-driven antioxidant signaling in response to in utero UFP exposure exacerbates pulmonary T cell skewing and induces pro-inflammatory effects and transcriptomic changes in fetal lung genes related to lipid metabolism and transport pathways, particularly in female offspring. In analogous work, we demonstrate the state of pregnancy also alters maternal pulmonary immune responses to UFPs and influenza, an important cause of respiratory viral infection in pregnant women. Results indicate UFP exposure during pregnancy increases susceptibility to and severity of influenza infection. Co-exposure results in decreased weight gain throughout pregnancy, elevation in viral titer and reduced lung inflammation, signifying immune suppression. Overall, findings emphasize common immunomodulatory effects from UFP exposure during pregnancy, on pregnant women and offspring, supporting interventions to protect these susceptible populations.
