Airway Macrophages Encompass Transcriptionally and Functionally Distinct Subsets Altered by Smoking

• Published in: American journal of respiratory cell and molecular biology Vol. 67; no. 2; pp. 241 - 252
• Main Authors: Liégeois, Maude, Bai, Qiang, Fievez, Laurence, Pirottin, Dimitri, Legrand, Céline, Guiot, Julien, Schleich, Florence, Corhay, Jean-Louis, Louis, Renaud, Marichal, Thomas, Bureau, Fabrice
• Format: Journal Article Web Resource
• Language: English
• Published: United States American Thoracic Society 01.08.2022
• Subjects: adult; airway macrophages; Airway management; Alveoli; autofluorescence; bronchoalveolar lavage fluid; bulk RNA sequencing; Cardiovascular & respiratory systems; chronic obstructive lung disease; Chronic obstructive pulmonary disease; clinical article; COPD; current smoker; detoxification; female; Flow cytometry; Fluid flow; Homeostasis; human; Human health sciences; Humans; immunoregulation; interleukin 10; lifespan; lung; lung alveolus macrophage; Lung diseases; macrophage; Macrophages; Macrophages, Alveolar; male; middle aged; monocyte; Monocytes; non-smoker; Obstructive lung disease; Original Research; oxidative stress; Pulmonary Disease, Chronic Obstructive; Respiratory tract; RNA sequencing; Sciences de la santé humaine; single cell RNA seq; single-cell and bulk RNA-seq; Smoking; Systèmes cardiovasculaire & respiratoire; bulk and single cell RNA-seq; Lung; smoking; Airway macrophage; COPD
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2021-0563OC

Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity and whose diversity in health and disease is a subject of intense investigations. Yet, it remains unclear to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Here, we aimed to explore heterogeneity of human AM isolated from healthy non-smokers, non-COPD smokers and COPD smokers by analyzing bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell RNA-sequencing. We found that subpopulations of BALF CD206+ macrophages could be distinguished based on their level of auto-fluorescence in each subject analyzed. CD206+ autofluorescenthigh (AFhi) AM were identified as classical, self-proliferative AM, while autofluorescentlow (AFlo) AM were expressing both monocyte- and classical AM-related genes, supportive of a monocytic origin. Of note, monocyte-derived AFlo AM exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Interestingly, single cell RNA-sequencing analyses showed that transcriptionally distinct clusters of classical and monocyte-derived AM were uniquely enriched in non-COPD and COPD smokers as compared to healthy non-smokers. Of note, such smoking-associated clusters exhibited gene signatures enriched in detoxification, oxidative stress and pro-inflammatory responses. Our study independently confirms previous reports supporting that monocyte-derived macrophages co-exist with classical AM in the airways of healthy subjects and COPD patients, and identifies smoking-associated changes in the AM compartment that may favor COPD initiation or progression.