RT info:eu-repo/semantics/article
T1 Tricarboxylic acid cycle activity and remodeling of glycerophosphocholine lipids support cytokine induction in response to fungal patterns
A1 Márquez Piñeiro, Saioa
A1 Fernández, José Javier
A1 Mancebo Tejera, Cristina
A1 Herrero Sánchez, María del Carmen
A1 Alonso Martín, Sara
A1 Sandoval, Tito Alejandro
A1 Rodríguez Prados, Macarena
A1 Cubillos Ruiz, Juan R.
A1 Montero Domínguez, Olimpio
A1 Fernández García, María Nieves
A1 Sánchez Crespo, Mariano
K1 Tricarboxylic acid cycle
K1 Cytokines
K1 Fungi
K1 Immunometabolism
K1 2302.21 Biología Molecular
K1 2302 Bioquímica
AB 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.
PB Cell Press
SN 2211-1247
YR 2019
FD 2019
LK https://uvadoc.uva.es/handle/10324/55101
UL https://uvadoc.uva.es/handle/10324/55101
LA eng
NO Cell Reports, 2019, Vol. 27, Nº. 2, págs. 525-536
NO Producción Científica
DS UVaDOC
RD 01-may-2024