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

Autor: Ivan Ramirez-Moral, Alex R. Schuurman, Christine C.A. van Linge, Joe M. Butler, Xiao Yu, Karen de Haan, Sarah van Leeuwen, Alex F. de Vos, Menno D. de Jong, Felipe A. Vieira Braga, Tom van der Poll
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 9, Pp 110662- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.110662
Popis: Summary: 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.
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