title: Tobacco exposure and susceptibility to tuberculosis: is there a smoking gun?
abstract: In many regions of the world, there is a great overlap between the prevalence of cigarette smoke exposure and tuberculosis. Despite the large body of epidemiologic evidence that tobacco smoke exposure is associated with increased tuberculosis infection, active disease, severity of disease, and mortality from tuberculosis, these studies cannot distinguish whether the mechanism is principally through direct impairment of anti-tuberculosis immunity by cigarette smoke or due to potential confounders that increase risk for tuberculosis and are commonly associated with smoking--such as poverty, malnutrition, and crowded living conditions. While there are several in vivo murine and in vitro macrophage studies showing cigarette smoke impairs control of tuberculous infection, little is known of the molecular and cellular mechanisms by which this impairment occurs. Herein, we highlight the key findings of these studies. Additionally, we review key immune cells that play critical roles in host-defense or pathogenesis of tuberculosis and generate a hypothesis-driven discussion of the possible mechanisms by which cigarette smoke impairs or enhances their functions, respectively, ultimately resulting in compromised immunity against tuberculosis.
authors.affiliation: Department of Medicine, Denver Veterans Affairs Medical Center, 1055 Clermont St, Denver, CO 80220, USA; Departments of Medicine and Academic Affairs, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Research 2, Box C-272, 9th Floor, 12700 East 19th Avenue, Aurora, CO 80045, USA. Electronic address: chane@njhealth.org.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Chan
authors.affiliation: Departments of Medicine and Academic Affairs, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Kinney
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Research 2, Box C-272, 9th Floor, 12700 East 19th Avenue, Aurora, CO 80045, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Honda
authors.affiliation: Departments of Medicine and Academic Affairs, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.
authors.forename: Raju
authors.initials: R
authors.lastname: Bishwakarma
authors.affiliation: Departments of Medicine and Academic Affairs, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.
authors.forename: Avani
authors.initials: A
authors.lastname: Gangavelli
authors.affiliation: Departments of Medicine and Academic Affairs, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Mya
authors.affiliation: Departments of Medicine and Academic Affairs, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Bai
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Ordway
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology
keywords: Air-pollution; Cigarette smoke; Host-defense; Mycobacterium tuberculosis