Cigarette smoking increases not only the risk of progression to active pulmonary TB disease, but also the risk of new TB infection, suggesting defective early response mechanisms in smokers. Smokers’ alveolar macrophages phagocytose bacteria and yeast normally and have normal bactericidal activity against M. tuberculosis. The incapacitation of alveolar macrophages by tobacco smoke particulates may contribute to increased risk of infection in two ways: (1) delayed time to phagocytosis by the alveolar macrophage, allowing for a longer extracellular growth period by the bacteria, and (2) increased chance of initial phagocytosis by a recruited, growth-permissive macrophage.

In addition to providing an explanation for the increased susceptibility of individuals with genetic lysosomal storage disorders to respiratory, skin, and mucosal infections, our findings may constitute a basis for the susceptibility of smokers to other respiratory infections, Finally, this mechanism may also contribute to the poorly understood association between indoor air pollution and TB.Smokers’ increased susceptibility to infection may be reversible..........