The study shows that nicotine, the main active chemical in cigarettes, can weaken the lung's natural defenses by lowering the production of antimicrobial peptides like LL-37, HBD‑2, and HBD‑3. This reduction lets the tuberculosis bacteria grow more easily inside certain lung cells.

Several epidemiological studies have identified the cigarette smoke as a risk factor for the infection and development of tuberculosis. Nicotine is considered the main immunomodulatory molecule of the cigarette. In the present study, we evaluated the effect of nicotine in the growth of M. tuberculosis. Lung epithelial cells and macrophages were infected with M. tuberculosis and/or treated with nicotine. The results show that nicotine increased the growth of M. tuberculosis mainly in type II pneumocytes (T2P) but not in airway basal epithelial cells nor macrophages. Further, it was observed that nicotine decreased the production of β-defensin-2, β-defensin-3, and the cathelicidin LL-37 in all the evaluated cells at 24 and 72 h post-infection. The modulation of the expression of antimicrobial peptides appears to be partially mediated by the nicotinic acetylcholine receptor α7 since the blockade of this receptor partially reverted the production of antimicrobial peptides. In summary, it was found that nicotine decreases the production of HBD-2, HBD-3, and LL-37 in T2P during the infection with M. tuberculosis promoting its intracellular growth.