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.
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.
Entities:
Keywords:
Respiratory Infection; Tobacco and the Lung; Tuberculosis
Authors: S Madretsma; L M Wolters; J P van Dijk; C J Tak; C Feyerabend; J H Wilson; F J Zijlstra Journal: Eur J Gastroenterol Hepatol Date: 1996-10 Impact factor: 2.566
Authors: Claire Healy; Natalia Munoz-Wolf; Janné Strydom; Lynne Faherty; Niamh C Williams; Sarah Kenny; Seamas C Donnelly; Suzanne M Cloonan Journal: Respir Res Date: 2021-04-29
Authors: Ma'en Obeidat; Xiaoting Ding; Nick Fishbane; Zsuzsanna Hollander; Raymond T Ng; Bruce McManus; Scott J Tebbutt; Bruce E Miller; Stephen Rennard; Peter D Paré; Don D Sin Journal: Nicotine Tob Res Date: 2016-05-06 Impact factor: 4.244
Authors: Xiyuan Bai; Jerry A Stitzel; An Bai; Cristian A Zambrano; Matthew Phillips; Philippa Marrack; Edward D Chan Journal: Am J Respir Cell Mol Biol Date: 2017-09 Impact factor: 6.914
Authors: Alexis D Payton; Alexia N Perryman; Jessica R Hoffman; Vennela Avula; Heather Wells; Carole Robinette; Neil E Alexis; Ilona Jaspers; Julia E Rager; Meghan E Rebuli Journal: Am J Physiol Lung Cell Mol Physiol Date: 2022-03-23 Impact factor: 5.464
Authors: Ilona E Keller; Oliver Vosyka; Shinji Takenaka; Alexander Kloß; Burkhardt Dahlmann; Lianne I Willems; Martijn Verdoes; Hermen S Overkleeft; Elisabeth Marcos; Serge Adnot; Stefanie M Hauck; Clemens Ruppert; Andreas Günther; Susanne Herold; Shinji Ohno; Heiko Adler; Oliver Eickelberg; Silke Meiners Journal: Sci Rep Date: 2015-05-19 Impact factor: 4.379