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Título
Tricarboxylic acid cycle activity and remodeling of glycerophosphocholine lipids support cytokine induction in response to fungal patterns
Autor
Año del Documento
2019
Editorial
Cell Press
Descripción
Producción Científica
Documento Fuente
Cell Reports, 2019, Vol. 27, Nº. 2, págs. 525-536
Abstract
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.
Materias Unesco
2302.21 Biología Molecular
2302 Bioquímica
Palabras Clave
Tricarboxylic acid cycle
Cytokines
Fungi
Immunometabolism
ISSN
2211-1247
Revisión por pares
SI
Patrocinador
Plan Nacional de Salud y Farmacia (Proyectos SAF2013-44521-R, SAF2017-83079-R, BFU2014-53469-P
Junta de Castilla y León - Fondo Social Europeo (Proyecto CSI035P17)
Junta de Castilla y León - Fondo Social Europeo (Proyecto CSI035P17)
Version del Editor
Propietario de los Derechos
© 2019 The Author(s)
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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