Airway Macrophages Encompass Transcriptionally and Functionally Distinct Subsets Altered by Smoking.
Maude A LiegeoisQiang BaiLaurence FievezDimitri PirottinCéline LegrandJulien GuiotFlorence SchleichJean-Louis CorhayRenaud LouisThomas MarichalFabrice BureauPublished in: American journal of respiratory cell and molecular biology (2022)
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 + autofluorescent high AMs were identified as classical, self-proliferative AM, whereas autofluorescent low AMs were expressing both monocyte and classical AM-related genes, supportive of a monocytic origin. Of note, monocyte-derived autofluorescent low 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.
Keyphrases
- chronic obstructive pulmonary disease
- single cell
- smoking cessation
- lung function
- endothelial cells
- induced apoptosis
- rna seq
- dendritic cells
- oxidative stress
- peripheral blood
- flow cytometry
- genome wide
- immune response
- public health
- high throughput
- cell cycle arrest
- mental health
- endoplasmic reticulum stress
- dna methylation
- signaling pathway
- gene expression
- transcription factor
- heat shock protein