Journal Article

Airway Macrophages Encompass Transcriptionally and Functionally Distinct Subsets Altered by Smoking

Fievez, Laurence, Guiot, Julien, Marichal, Thomas, Bureau, Fabrice, Liégeois, Maude, Bai, Qiang, Pirottin, Dimitri, Legrand, Céline, Schleich, Florence, Corhay, Jean-Louis, Louis, Renaud

2022

Overview

Abstract Alveolar macrophages (AMs) 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 AMs isolated from healthy nonsmokers, smokers without COPD, and smokers with COPD by analyzing BAL fluid cells by flow cytometry and bulk and single-cell RNA sequencing. We found that subpopulations of BAL fluid CD206+ macrophages could be distinguished based on their degree of autofluorescence in each subject analyzed. CD206+ autofluorescenthigh AMs were identified as classical, self-proliferative AM, whereas autofluorescentlow AMs were expressing both monocyte and classical AM-related genes, supportive of a monocytic origin. Of note, monocyte-derived autofluorescentlow AMs exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine IL-10. Interestingly, single-cell RNA-sequencing analyses showed that transcriptionally distinct clusters of classical and monocyte-derived AM were uniquely enriched in smokers with and without COPD as compared with healthy nonsmokers. Of note, such smoking-associated clusters exhibited gene signatures enriched in detoxification, oxidative stress, and proinflammatory responses. Our study independently confirms previous reports supporting that monocyte-derived macrophages coexist with classical AM in the airways of healthy subjects and patients with COPD and identifies smoking-associated changes in the AM compartment that may favor COPD initiation or progression.

• Publisher: Oxford University Press,American Thoracic Society
• Subject: 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