Fungal Patterns Induce Cytokine Expression through Fluxes of Metabolic Intermediates That Support Glycolysis and Oxidative Phosphorylation.
J Immunol
; 208(12): 2779-2794, 2022 06 15.
Article
in En
| MEDLINE
| ID: mdl-35688467
ABSTRACT
Cytokine expression is fine-tuned by metabolic intermediates, which makes research on immunometabolism suitable to yield drugs with a wider prospect of application than the biological therapies that block proinflammatory cytokines. Switch from oxidative phosphorylation (OXPHOS) to glycolysis has been considered a characteristic feature 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. Results showed that nucleocytosolic citrate and ATP-citrate lyase activity drove IL1B, IL10, and IL23A expression by yielding acetyl-CoA and oxaloacetate, with the latter one supporting glycolysis and OXPHOS by maintaining cytosolic NAD+ and mitochondrial NADH levels through mitochondrial shuttles. Succinate dehydrogenase showed a subunit-specific ability to modulate IL23A and IL10 expression. Succinate dehydrogenase A subunit activity supported cytokine expression through the control of the 2-oxoglutarate/succinate ratio, whereas C and D subunits underpinned cytokine expression by conveying electron flux from complex II to complex III of the electron transport chain. Fatty acids may also fuel the tricarboxylic acid cycle and influence cytokine expression. Overall, these results show that fungal patterns support cytokine expression through a strong boost of glycolysis and OXPHOS supported by the use of pyruvate, citrate, and succinate, along with the compartmentalized NAD(H) redox state maintained by mitochondrial shuttles.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidative Phosphorylation
/
Succinate Dehydrogenase
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
2022
Type:
Article
Affiliation country:
Spain