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Original article
Cigarette smoke impairs cytokine responses and BCG containment in alveolar macrophages
  1. Richard N van Zyl-Smit1,
  2. Anke Binder1,
  3. Richard Meldau1,
  4. Patricia L Semple1,
  5. Alicia Evans2,
  6. Peter Smith2,
  7. Eric D Bateman1,
  8. Keertan Dheda1,3,4
  1. 1Lung Infection and Immunity Unit, Division of Pulmonology & UCT Lung Institute, Department of Medicine, University of Cape Town, South Africa
  2. 2Division of Pharmacology, Department of Medicine, University of Cape Town, South Africa
  3. 3Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa
  4. 4Department of Infection, University College London Medical School, UK
  1. Correspondence to Professor Keertan Dheda, Groote Schuur Hospital, H47 Old Main Building, Observatory, 7925, South Africa; keertan.dheda{at}uct.ac.za

Abstract

Background There is a strong epidemiological link between smoking and tuberculosis (TB), but the association is confounded by socioeconomic and other factors. A direct relationship between cigarette smoke and poor treatment-related outcomes in patients with TB is therefore questionable. We investigated whether constituents of tobacco smoke impair mycobacterial host immune responses in vitro.

Methodology Preparation of a cigarette smoke extract (CSE) from Marlboro Red cigarettes was standardised and reproducibility verified by mass spectroscopy. Macrophages were derived from peripheral blood monocytes (MDM) and alveolar macrophages from bronchoalveolar lavage fluid from healthy non-smoking volunteers. Mycobacterial uptake (flow cytometric detection of fluorescence using green fluorescent protein-labelled BCG), cytokine responses (ELISA) and mycobacterial containment (colony forming units) was evaluated in both macrophage populations with and without co-culture with CSE, nicotine and a nicotine receptor blocker.

Results Cigarette smoke failed to impair the uptake of mycobacteria by monocyte-derived or alveolar macrophages. CSE (vs no CSE) reduced the mean (SD) BCG-driven macrophage (MDM) interferon γ (IFN-γ), tumour necrosis factor α (TNF-α) and interleukin 10 (IL-10) responses by 56.4 (18.6)%, 67.0 (33.4)% and 77.7 (27.7)%, respectively (p<0.001). Nicotine alone impaired IL-10 and TNF-α production by 48.8 (37)% and 49 (50)%, respectively (p<0.05) through an α-7 nicotine receptor-independent mechanism. In 5-day cultures, CSE impaired mycobacterial (BCG) containment in both monocyte-derived and alveolar macrophages.

Conclusions Cigarette smoke attenuates effector cytokine responses and impairs mycobacterial containment within infected human macrophages derived from the peripheral blood and alveolar compartments, thus supporting the hypothesis that cigarette smoke subverts mycobacteria-related immunity.

  • Tuberculosis
  • Tobacco and the Lung
  • Respiratory Infection

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