Journal article
Tobacco smoke exposure recruits inflammatory airspace monocytes that establish permissive lung niches for Mycobacterium tuberculosis
Science translational medicine, Vol.15(725), eadg3451
12/06/2023
DOI: 10.1126/scitranslmed.adg3451
PMCID: PMC12289333
PMID: 38055798
Abstract
Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive to Mycobacterium tuberculosis (Mtb) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current and never smokers by performing single-cell RNA sequencing (scRNA-seq), flow cytometry, and functional assays. We observed the enrichment of immature inflammatory monocytes in the lungs of smokers compared with nonsmokers. These monocytes exhibited phenotypes consistent with recent recruitment from blood, ongoing differentiation, increased activation, and states similar to those with chronic obstructive pulmonary disease. Using integrative scRNA-seq and flow cytometry, we identified CD93 as a marker for a subset of these newly recruited smoking-associated lung monocytes and further provided evidence that the recruitment of monocytes into the lung was mediated by CCR2-binding chemokines, including CCL11. We also show that these cells exhibit elevated inflammatory responses upon exposure to Mtb and accelerated intracellular growth of Mtb compared with mature macrophages. This elevated Mtb growth could be inhibited by anti-inflammatory small molecules, providing a connection between smoking-induced pro-inflammatory states and permissiveness to Mtb growth. Our findings suggest a model in which smoking leads to the recruitment of immature inflammatory monocytes from the periphery to the lung, which results in the accumulation of these Mtb-permissive cells in the airway. This work defines how smoking may lead to increased susceptibility to Mtb and identifies host-directed therapies to reduce the burden of TB among those who smoke.
Details
- Title: Subtitle
- Tobacco smoke exposure recruits inflammatory airspace monocytes that establish permissive lung niches for Mycobacterium tuberculosis
- Creators
- Björn Corleis - Friedrich-Loeffler-InstitutConstantine N Tzouanas - Ragon Institute of MGH, MIT and HarvardMarc H Wadsworth - Broad InstituteJosalyn L Cho - University of IowaAlice H Linder - Ragon Institute of MGH, MIT and HarvardAbigail E Schiff - Brigham and Women's HospitalBjörn Zessin - Friedrich-Loeffler-InstitutFabian Stei - Friedrich-Loeffler-InstitutAnca Dorhoi - Friedrich-Loeffler-InstitutAmy K Dickey - Ragon Institute of MGH, MIT and HarvardBenjamin D Medoff - Massachusetts General HospitalAlex K Shalek - Ragon Institute of MGH, MIT and HarvardDouglas S Kwon - Massachusetts General Hospital
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.15(725), eadg3451
- DOI
- 10.1126/scitranslmed.adg3451
- PMID
- 38055798
- PMCID
- PMC12289333
- NLM abbreviation
- Sci Transl Med
- eISSN
- 1946-6242
- Language
- English
- Date published
- 12/06/2023
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984520559202771
Metrics
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