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A4456 - Age-Related Modulation of Pulmonary Innate Immunity by Environmental Tobacco Smoke Against Influenza A/PR/8/34 in Mice
Author Block: M. Rajavel1, L. Wang2, M. Poindexter1, T. Mar1, C. B. Fulgar1, J. Singh1, K. E. Pinkerton1; 1Center for Health and the Environment, University of California, Davis, Davis, CA, United States, 2Internal Medicine, University of California, Davis, Davis, CA, United States.
Rationale: Limited research exists to describe how environmental stressors such as environmental tobacco smoke (ETS) influences the sensitivity of neonates to viral infection and their subsequent ability to mount a sufficient immune response. Objective: The purpose of this study was to determine the effects of ETS exposure on the neonatal immune response to influenza virus infection and to characterize any differences in ETS effects apparent between neonatal and adult individuals. Methods: A 6-week exposure to either ETS (1.0 mg/m3) or filtered air (FA) was carried out on neonatal (from gestational day 14 to 5 weeks post-natal age) and adult (from 9 to 15 weeks of age) BALB/c mice. Mice were then inoculated with murine influenza A/PR8 (TCID50 of 12.6) or vehicle (PBS) via nasal aspiration. Lung and spleen tissue were collected day 7 post infection for analysis. Results: Following ETS exposure, neonates infected with influenza exhibited an increased inflammatory response in the lungs compared to virally infected adults. ETS-virus neonates demonstrated a robust recruitment of macrophages to the lungs, significantly more than their adult counterparts. In addition, a significant increase in CD4 Helper T-cells in ETS-virus neonates compared to ETS-virus adults was observed via immunohistochemistry. Comparison of ETS exposed and FA exposed neonates infected with influenza indicated a significant shift in the inflammatory response to the viral challenge. The local immune response was characterized by an increase in lymphocytes, particularly CD4+ T-cells to the lung, resulting in heightened inflammation in lung parenchyma evidenced by histopathology. Systemic immune changes were observed and defined by a significant upregulation of IFNy and Type 1 IFN mRNA expression in the spleen following ETS exposure. Conclusion: Neonatal ETS exposure induces a divergent inflammatory profile, both local and systemic, during influenza virus infection in BALB/c mice. Compared to FA exposed neonates, neonates exposed to ETS exhibit significant increases in lung inflammation which could be as a result of heightened lymphocyte recruitment to lung tissue, particularly that of CD4+ helper T-cells. Additionally, exposure of ETS during neonatal development induces an immunological shift defined by increased lymphocyte recruitment to the lungs during influenza infection- a trend which is not seen in ETS exposed adults. This indicates that ETS exposure affects the neonatal and adult immune systems differentially. Future research should focus on further characterization of the CD4+ T-cells into phenotypic and functional subsets to determine more precisely the role these cells play in the observed ETS-induced immunological changes.