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Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection
Horvath, K., M. Brighton, W. Zhang, J. Carson, AND I. Jaspers. Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 45(2):237-45, (2011).
This manuscript was orginally approved via paper cleareance EPHD-12-057 and entered in the Science Inventory
Epidemiologic evidence suggests that cigarette smoking is a risk factor for infection with influenza, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers demonstrate a decreased ability to orchestrate an influenza-induced immune response, we established a model using differentiated nasal epithelial cells (NECs) from nonsmokers and smokers, co-cultured with peripheral blood monoe derived dendritic cells (mono-DCs) from nonsmokers. NEC/mono-DC co-cultures were infected with influenza A vin analyzed for influenza-induced immune responses 24 hours after infection. We observed that NECs from smokers" as mono-DCs co-cultured with NECs from smokers, exhibited suppressed influenza-induced, interferon-related pre interferon regulatory factor-7, Toll-like receptor-3, and retinoic acid inducible gene-1, likely because of the suppressed production of IFNa from the NECs of smokers. Furthermore, NEC/mono-DC co-cultures using NECs from smokers exhibited suppressed concentrations of T-cell/natural killer cell chemokine interferon gamma-induced protein 10 (IP10)after infection with influenza, indicating that NECs from smokers may skew early influenza-induced Thl responses. In contrast, NEC/mono-DC co-cultures using NEC from smokers contained increased influenza-induced concentration the Th2 chemokine thymic stromal lymphopoeitin (TSLP). In addition, NECs from smokers cultured alone had increa: influenza-induced concentrations of the Th2 chemokine thymus and activation-regulated chemokine (TARC). Using model, we demonstrated that in the context of infection with influenza, NECs obtained from smokers create an over cytokine microenvironment that suppresses the interferon-mediated Thl response and enhances the TSLP-TARC-mediated Th2 response, with the potential to modify the responses of DCs. Smoking-induced alterations in the Th1 balance may play a role in developing underlying susceptibilities to respiratory vira