Effects of life-stage and passive tobacco smoke exposure on pulmonary innate immunity and influenza infection in mice

Limited data are available on the effects of perinatal environmental tobacco smoke (ETS) exposure for early childhood influenza infection. The aim of the present study was to examine whether perinatal versus adult ETS exposure might provoke more severe systemic and pulmonary innate immune responses in mice inoculated with influenza A/Puerto Rico/8/34 virus (IAV) compared to phosphate-buffered saline (PBS). BALB/c mice were exposed to filtered air (FA) or ETS for 6 weeks during the perinatal or adult period of life. Immediately following the final exposure, mice were intranasally inoculated with IAV or PBS. Significant inflammatory effects were observed in bronchoalveolar lavage fluid of neonates inoculated with IAV (FA+IAV or ETS+IAV) compared to PBS (ETS+PBS or FA+PBS), and in the lung parenchyma of neonates administered ETS+IAV versus FA+IAV. Type I and III interferons were also elevated in the spleens of neonates, but not adults with ETS+IAV versus FA+IAV exposure. Both IAV-inoculated neonate groups exhibited significantly more CD4 T cells and increasing numbers of CD8 and CD25 T cells in lungs relative to their adult counterparts. Taken together, these results suggest perinatal ETS exposure induces an exaggerated innate immune response, which may overwhelm protective anti-inflammatory defenses against IAV, and enhances severity of infection at early life stages (e.g., in infants and young children).