title: Cigarette smoke increases susceptibility to tuberculosis--evidence from in vivo and in vitro models.
abstract: BACKGROUND
  Cigarette smoke (CS) exposure is an epidemiological risk factor for tuberculosis, although the biological basis has not been elucidated.
  
  
  METHODS
  We exposed C57BL/6 mice to CS for 14 weeks and examined their ability to control an aerosol infection of Mycobacterium tuberculosis Erdman.
  
  
  RESULTS
  CS-exposed mice had more M. tuberculosis isolated from the lungs and spleens after 14 and 30 d, compared with control mice. The CS-exposed mice had worse lung lesions and less lung and splenic macrophages and dendritic cells (DCs) producing interleukin12 and tumor necrosis factor α (TNF-α). There were significantly more interleukin 10-producing macrophages and DCs in the spleens of infected CS-exposed mice than in non-CS-exposed controls. CS-exposed mice also showed a diminished influx of interferon γ-producing and TNF-α-producing CD4(+) and CD8(+) effector and memory T cells into the lungs and spleens. There was a trend toward an increased number of viable intracellular M. tuberculosis in macrophages isolated from humans who smoke compared with nonsmokers. THP-1 human macrophages and primary human alveolar macrophages exposed to CS extract, nicotine, or acrolein showed an increased burden of intracellular M. tuberculosis.
  
  
  CONCLUSIONS
  CS suppresses the protective immune response to M. tuberculosis in mice, human THP-1 cells, and primary human alveolar macrophages.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Shang
authors.forename: Diane
authors.initials: D
authors.lastname: Ordway
authors.forename: Marcela
authors.initials: M
authors.lastname: Henao-Tamayo
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Rebecca
authors.initials: R
authors.lastname: Oberley-Deegan
authors.forename: Crystal
authors.initials: C
authors.lastname: Shanley
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
authors.forename: Stephanie
authors.initials: S
authors.lastname: Case
authors.forename: Maisha
authors.initials: M
authors.lastname: Minor
authors.forename: David
authors.initials: D
authors.lastname: Ackart
authors.forename: Laurel
authors.initials: L
authors.lastname: Hascall-Dove
authors.forename: Alida R
authors.initials: AR
authors.lastname: Ovrutsky
authors.forename: Pitchaimani
authors.initials: P
authors.lastname: Kandasamy
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.forename: Cherie
authors.initials: C
authors.lastname: Lambert
authors.forename: Brian M
authors.initials: BM
authors.lastname: Freed
authors.forename: Michael D
authors.initials: MD
authors.lastname: Iseman
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: Edward D
authors.initials: ED
authors.lastname: Chan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012907:Smoking / Q000009:adverse effects*; D014376:Tuberculosis / Q000276:immunology*