Home > Cigarette smoking impairs human pulmonary immunity to mycobacterium tuberculosis.

O'Leary, Seónadh M and Coleman, Michelle M and Chew, Wui Mei and Morrow, Colette and McLaughlin, Anne Marie and Gleeson, Laura E and O'Sullivan, Mary P and Keane, Joseph (2014) Cigarette smoking impairs human pulmonary immunity to mycobacterium tuberculosis. American Journal of Respiratory and Critical Care Medicine, 190, (12), pp. 1430-1436. doi: 10.1164/rccm.201407-1385OC.

Rationale: Cigarette smoking is linked to important aspects of tuberculosis, such as susceptibility to infection, disease reactivation, mortality, transmission and persistent infectiousness. The mechanistic basis for this remains poorly understood.

Objectives: To compare the functional impairment, seen in human alveolar macrophages (AM) from non-smokers, smokers and ex-smokers, after infection with Mycobacterium tuberculosis (Mtb).

Methods: AM were acquired at bronchoscopy, number and viability from smoking donors were compared to non-smoking donors. AM were challenged in vitro with Mtb and intracellular bacterial viability was measured. Cytokine secretion was measured 24hrs post-infection by ELISA. Previously we determined the frequency of CD4+FoxP3+ T cells in the presence or absence of allogeneic AM, data was reanalysed to separate the patient subjects according to smoking status.

Measurements and Main Results: There were significantly more AM from smokers compared to non-smokers or ex-smokers (p<0.01). AM from smokers could not control intracellular Mtb growth. Non-smokers' AM generated significantly more TNF-α, IFN-γ and IL-1β following Mtb infection compared to uninfected (p<0.05). However Mtb-infected AM from smokers did not secrete significantly more TNF-α, IFN-γ and IL-1β compared to uninfected smokers' AM. AM taken from ex-smokers also failed to secrete significantly increased TNF-α, IFN-γ and IL-1β after Mtb infection. Both smokers' and non-smokers' AM induced FoxP3+ T regulatory (Treg) cell phenotype responses in allogeneic admixed T-cells (>4.8 fold, p<0.05). Even after Mtb infection, AM continued to drive this regulatory phenotype.

Conclusions: In smokers, the pulmonary compartment has a number of macrophage-specific immune impairments which provide some mechanistic explanations whereby cigarette smoking renders a patient susceptible to tuberculosis infection and disease.

Item Type
Publication Type
Irish-related, International, Article
Drug Type
Tobacco / Nicotine
Intervention Type
Harm reduction
12 November 2014
Identification #
doi: 10.1164/rccm.201407-1385OC
Page Range
pp. 1430-1436
American Thoracic Society
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