mTOR-driven glycolysis governs induction of innate immune responses by bronchial epithelial cells exposed to the bacterial component flagellin

Human bronchial epithelial (HBE) cells play an essential role during bacterial infections of the airways by sensing pathogens and orchestrating protective immune responses. We here sought to determine which metabolic pathways are utilized by HBE cells to mount innate immune responses upon exposure t...

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Bibliographic Details
Published in:Mucosal immunology Vol. 14; no. 3; pp. 594 - 604
Main Authors: Ramirez-Moral, I., Yu, X., Butler, J.M., van Weeghel, M., Otto, N.A., Ferreira, B. Lima, Maele, L. Van, Sirard, J.C., de Vos, A.F., de Jong, M.D., Houtkooper, R.H., van der Poll, T.
Format: Journal Article
Language:English
Published: New York Elsevier Inc 01.05.2021
Nature Publishing Group US
Elsevier Limited
Nature Pub. Group
Subjects:
Allergology
Animals
Antibodies
Bacteria
Bacterial infections
Biomedical and Life Sciences
Biomedicine
Bronchi - pathology
Cells, Cultured
Cellular Reprogramming
Disease Models, Animal
Epithelial cells
Epithelial Cells - immunology
Epithelium
Female
Flagellin
Flagellin - metabolism
Gastroenterology
Glycolysis
Humans
Immune response
Immunity, Innate
Immunology
Innate immunity
Klebsiella Infections - immunology
Klebsiella pneumoniae - physiology
Life Sciences
Metabolic pathways
Metabolism
Mice
Mice, Inbred C57BL
Mucosal immunity
Pseudomonas aeruginosa - physiology
Pseudomonas Infections - immunology
Rapamycin
Respiratory tract
TOR protein
TOR Serine-Threonine Kinases - metabolism
ISSN:1933-0219, 1935-3456, 1935-3456
Online Access:Get full text
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Summary:Human bronchial epithelial (HBE) cells play an essential role during bacterial infections of the airways by sensing pathogens and orchestrating protective immune responses. We here sought to determine which metabolic pathways are utilized by HBE cells to mount innate immune responses upon exposure to a relevant bacterial agonist. Stimulation of HBE cells by the bacterial component flagellin triggered activation of the mTOR pathway resulting in an increased glycolytic flux that sustained the secretory activity of immune mediators by HBE cells. The mTOR inhibitor rapamycin impeded glycolysis and limited flagellin-induced secretion of immune mediators. The role of the mTOR pathway was recapitulated in vivo in a mouse model of flagellin-triggered lung innate immune responses. These data demonstrate that metabolic reprogramming via the mTOR pathway modulates activation of the respiratory epithelium, identifying mTOR as a potential therapeutic target to modulate mucosal immunity in the context of bacterial infections.
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ISSN:1933-0219
1935-3456
1935-3456
DOI:10.1038/s41385-021-00377-8