RT info:eu-repo/semantics/doctoralThesis
T1 La reprogramación metabólica inducida por patrones moleculares de la pared fúngica regula la expresión de citoquinas
A1 Mancebo Tejera, Cristina
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Metabolismo - Inmunología
K1 Immunometabolism
K1 Inmunometabolismo
K1 2403 Bioquímica
K1 2415 Biología Molecular
AB Switch from OXPHOS to glycolysis is considered a characteristic of activated immune cells. However, some stimuli might enhance both routes concomitantly. The connection between the tricarboxylic acid cycle and cytokine expression was scrutinized in human monocyte-derived dendritic cells stimulated with the fungal surrogate zymosan. Nucleocytosolic citrate drove IL1B, IL10, and IL23A expression by yielding acetyl-CoA and oxaloacetate, the latter one supporting glycolysis and OXPHOS by maintaining cytosolic NAD+ and mitochondrial NADH levels through mitochondrial shuttles. Succinate dehydrogenase (SDH) showed a subunit-specific ability to modulate cytokine expression. SDHA activity supported cytokine expression through the control of 2-oxoglutarate/succinate ratio, while SDHC and SDHD underpinned cytokine expression through electron flux from complex II to complex III of the electron transport chain. These results show that fungal patterns support cytokine expression through glycolysis and OXPHOS supported by pyruvate, citrate, and succinate, along with the compartmentalized NAD(H) redox state maintained by mitochondrial shuttles.
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/59773
UL https://uvadoc.uva.es/handle/10324/59773
LA spa
NO Escuela de Doctorado
DS UVaDOC
RD 17-jul-2024