Cigarette smoke increases susceptibility to tuberculosis-evidence from in vivo and in vitro models

Shaobin Shang, Diane Ordway, Marcela Henao-Tamayo, Xiyuan Bai, Rebecca Oberley-Deegan, Crystal Shanley, Ian M. Orme, Stephanie Case, Maisha Minor, David Ackart, Laurel Hascall-Dove, Alida R. Ovrutsky, Pitchaimani Kandasamy, Dennis R. Voelker, Cherie Lambert, Brian M. Freed, Michael D. Iseman, Randall J. Basaraba, Edward D. Chan

Research output: Contribution to journalArticle

70 Scopus citations

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. Conclusion: CS suppresses the protective immune response to M. tuberculosis in mice, human THP-1 cells, and primary human alveolar macrophages.

Original languageEnglish (US)
Pages (from-to)1240-1248
Number of pages9
JournalJournal of Infectious Diseases
Volume203
Issue number9
DOIs
StatePublished - May 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Shang, S., Ordway, D., Henao-Tamayo, M., Bai, X., Oberley-Deegan, R., Shanley, C., Orme, I. M., Case, S., Minor, M., Ackart, D., Hascall-Dove, L., Ovrutsky, A. R., Kandasamy, P., Voelker, D. R., Lambert, C., Freed, B. M., Iseman, M. D., Basaraba, R. J., & Chan, E. D. (2011). Cigarette smoke increases susceptibility to tuberculosis-evidence from in vivo and in vitro models. Journal of Infectious Diseases, 203(9), 1240-1248. https://doi.org/10.1093/infdis/jir009