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

Autor(es):Mostrar menos -

Ramirez-Moral, I ^[1] ; Yu, X. ^[2] ; Butler, J. M. ^[1] ; van Weeghel, M. ^[3] ; Otto, N. A. ^[1] ; Ferreira, B. Lima ^[1] ; Van Maele, L. ^[4] ; Sirard, J. C. ^[4] ; de Vos, A. F. ^[1] ; de Jong, M. D. ^[2] ; Houtkooper, R. H. ^[3] ; van der Poll, T. ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Amsterdam, Ctr Expt & Mol Med, Amsterdam UMC, Amsterdam - Netherlands

^[2] Univ Amsterdam, Dept Med Microbiol, Amsterdam UMC, Amsterdam - Netherlands

^[3] Univ Amsterdam, Amsterdam UMC, Amsterdam Cardiovasc Sci, Lab Genet Metab Dis, Amsterdam Gastroenterol & Met, Amsterdam - Netherlands

^[4] Univ Lille, CIIL Ctr Infect & Immun Lille, Inst Pasteur Lille, CNRS, Inserm, CHU Lille, UMR9017, U1019, Lille - France

^[5] Univ Amsterdam, Div Infect Dis, Amsterdam UMC, Amsterdam - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: MUCOSAL IMMUNOLOGY; v. 14, n. 3, p. 594-604, MAY 2021.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 19/02224-0 - Metabolismo de células epiteliais e células imunes das vias aéreas na homeostase e inflamação
• Beneficiário: Bianca Rodrigues Lima Ferreira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado