2026-07-16T10:44:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71532024-09-27T08:01:46Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Basit, Farhan
author
Mathan, Till
author
Sancho, David
author
de Vries, I Jolanda M
funder
Dutch Research Council (Holanda)
funder
Unión Europea. Comisión Europea
2019-02-11T07:45:52Z
2019-02-11T07:45:52Z
2018
Front Immunol. 2018; 9:2489
10.3389/fimmu.2018.02489
1664-3224
1664-3224
Frontiers in immunology
30455688
http://hdl.handle.net/20.500.12105/7153
Toll-like receptor (TLR) agonists induce metabolic reprogramming, which is required for immune activation. We have investigated mechanisms that regulate metabolic adaptation upon TLR-stimulation in human blood DC subsets, CD1c+ myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). We show that TLR-stimulation changes expression of genes regulating oxidative phosphorylation (OXPHOS) and glutamine metabolism in pDC. TLR-stimulation increases mitochondrial content and intracellular glutamine in an autophagy-dependent manner in pDC. TLR-induced glutaminolysis fuels OXPHOS in pDCs. Notably, inhibition of glutaminolysis and OXPHOS prevents pDC activation. Conversely, TLR-stimulation reduces mitochondrial content, OXPHOS activity and induces glycolysis in CD1c+ mDC. Inhibition of mitochondrial fragmentation or promotion of mitochondrial fusion impairs TLR-stimulation induced glycolysis and activation of CD1c+ mDCs. TLR-stimulation triggers BNIP3-dependent mitophagy, which regulates transcriptional activity of AMPKα1. BNIP3-dependent mitophagy is required for induction of glycolysis and activation of CD1c+ mDCs. Our findings reveal that TLR stimulation differentially regulates mitochondrial dynamics in distinct human DC subsets, which contributes to their activation.
eng
CD1c+ mDC
OXPHOS
Glutaminolysis
Glycolysis
Mitochondrial dynamics
Mitophagy
pDC
Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response
journal article
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HumanDendriticCellSubsets_2018.pdf.txt