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oai:uvadoc.uva.es:10324/551012023-02-28T10:39:34Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Tricarboxylic acid cycle activity and remodeling of glycerophosphocholine lipids support cytokine induction in response to fungal patterns Márquez Piñeiro, Saioa Fernández, José Javier Mancebo Tejera, Cristina Herrero Sánchez, María del Carmen Alonso Martín, Sara Sandoval, Tito Alejandro Rodríguez Prados, Macarena Cubillos Ruiz, Juan R. Montero Domínguez, Olimpio Fernández García, María Nieves Sánchez Crespo, Mariano Producción Científica Increased glycolysis parallels immune cell activation, but the role of pyruvate remains largely unexplored. We found that stimulation of dendritic cells with the fungal surrogate zymosan causes decreases of pyruvate, citrate, itaconate, and a-ketoglutarate, while increasing oxaloacetate, succinate, lactate, oxygen consumption, and pyruvate dehydrogenase activity. Expression of IL10 and IL23A (the gene encoding the p19 chain of IL-23) depended on pyruvate dehydrogenase activity. Mechanistically, pyruvate reinforced histone H3 acetylation, and acetate rescued the effect of mitochondrial pyruvate carrier inhibition, most likely because it is a substrate of the acetyl-CoA producing enzyme ACSS2. Mice lacking the receptor of the lipid mediator platelet-activating factor (PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) showed reduced production of IL-10 and IL-23 that is explained by the requirement of acetyl-CoA for PAF biosynthesis and its ensuing autocrine function. Acetyl-CoA therefore intertwines fatty acid remodeling of glycerophospholipids and energetic metabolism during cytokine induction. 2022-09-14T11:18:44Z 2022-09-14T11:18:44Z 2019 info:eu-repo/semantics/article Cell Reports, 2019, Vol. 27, Nº. 2, págs. 525-536 2211-1247 https://uvadoc.uva.es/handle/10324/55101 10.1016/j.celrep.2019.03.033 525 2 536.e4 Cell Reports 27 eng https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30349-3 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ © 2019 The Author(s) Attribution-NonCommercial-NoDerivatives 4.0 Internacional Cell Press SI