Modulation of airway epithelial responses to mycobacteria by acute cigarette smoke exposure

Exposure to cigarette smoke (CS) is a known risk factor for pulmonary tuberculosis, and smokers are at increased risk of treatment failure and relapse. Using differentiated primary human bronchial epithelial cells (PBEC), we studied whether there is a direct effect of CS exposure on epithelial host responses to infection with Mycobacterium tuberculosis (Mtb) and Mycobacterium avium (Mav). Intracellular mycobacterial infection in PBEC remained unchanged by acute pre-exposure to CS. Transcriptomic analyses revealed that pathways involved in cytokine and growth factor signalling were significantly affected in Mav-infected cells with prior CS exposure compared to air exposure. Overall, cytokine secretion was increased in uninfected CS-exposed PBEC, while it was decreased in infected cells. Marked inter-donor variations indicated that the baseline inflammatory status of individual donors may partially determine subsequent responses to CS exposure and infection. Finally, a single dose of CS resulted in a near-significant increase biofilm formation by Mtb but not Mav on the epithelium. Altogether, direct exposure of bronchial epithelial cells to CS had limited effects on host responses to infection at 7 days, did not affect mycobacterial levels, but may facilitate biofilm formation by Mtb.