Cigarette Smoke Alters Influenza-Induced Immune Responses of the Respiratory Epithelium

 

Trainee:

Katy Horvath

Horvath

Research Mentor:

Dr. Ilona Jaspers, PhD

jaspers

Clinical Co-Mentor;

Dr. Terry  Noah, MD

Noah
Project Description:

Epidemiological evidence has shown that smokers are more susceptible to viral infections than nonsmokers, but the mechanism of this vulnerability is poorly understood. Influenza A infection is more severe in smokers and results in a 44% increase in influenza related complications in smokers compared to nonsmokers. Anti-viral responses depend upon resident innate immune cells such as natural killer (NK) cells and dendritic cells (DCs). NK cells and DCs have intimate contact with epithelial cells of the respiratory epithelium and respond immediately to pathogenic insults to direct the localized innate immune response and mobilize the adaptive immune response that will ultimately clear a viral infection. Understanding how smoking alters the mechanics of this cell-cell communication between NK cells, DCs, and epithelial cells is crucial.

Our hypothesis is that cigarette smoke impairs the capability of epithelial cells to communicate with resident immune cells, like NK cells and DCs, and confers an enhanced susceptibility to viral infection. We will identify the responses of NK cells and DCs in the nasal epithelium of nonsmokers and smokers after inoculation with Flumist®, a live attenuated influenza vaccine (LAIV). NK-DC communication will be assessed by analyzing the production of cytokines by the epithelium in response to LAIV. Using a co-culture model of nasal epithelial cells (NEC) and DCs, we will determine the effects of in vivo cigarette smoke exposure on the responses of NEC and DCs to influenza infections. DCs are crucial antigen presenting cells that are important in initiating an adaptive T cell response. Effects of in vivo cigarette smoke exposure on both the initial and memory T cell response as a function of DC activity will be evaluated. This research will shed light on how cigarette smoke affects viral immunity and pave the way for future research of appropriate anti-viral therapeutics for cigarette smoke exposure.