Single-cell transcriptomics reveals subset-specific metabolic profiles underpinning the bronchial epithelial response to flagellin

• Published in: iScience Vol. 27; no. 9; p. 110662
• Main Authors: Ramirez-Moral, Ivan, Schuurman, Alex R., van Linge, Christine C.A., Butler, Joe M., Yu, Xiao, de Haan, Karen, van Leeuwen, Sarah, de Vos, Alex F., de Jong, Menno D., Vieira Braga, Felipe A., van der Poll, Tom
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.09.2024; Elsevier
• Subjects: Biochemistry; Cellular physiology; Physiology; Transcriptomics; Biochemistry; Physiology; Transcriptomics; Cellular physiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110662

Airway epithelial cells represent the first line of defense against respiratory pathogens. Flagellin drives the motility of many mucosal pathogens and has been suggested as an immune enhancing adjunctive therapeutic in infections of the airways. This study leveraged single-cell RNA sequencing to determine cell-specific effects of flagellin in primary human bronchial epithelial cells growing in air-liquid interface. Seven cell clusters were identified, including ciliated cells, ionocytes, and several states of basal and secretory cells, of which only inflammatory basal cells and inflammatory secretory cells demonstrated a proportional increase in response to flagellin. Inflammatory secretory cells showed evidence of metabolic reprogramming toward aerobic glycolysis, while in inflammatory basal cells transcriptome profiles indicated enhanced oxidative phosphorylation. Inhibition of mTOR prevented the shift to glycolysis and reduced inflammatory gene transcription specifically in inflammatory secretory cells. These data demonstrate the functional heterogeneity of the human airway epithelium upon exposure to flagellin. [Display omitted] •Single-cell RNA sequencing identified seven cell clusters in human airways•Flagellin selectively increased inflammatory basal and secretory cells•Flagellin enhanced aerobic glycolysis in inflammatory secretory cells•mTOR inhibition prevented glycolysis and reduced inflammation in this cell subset Biochemistry; Physiology; Cellular physiology; Transcriptomics