Basit, Farhan Mathan, Till Sancho, David Jolanda M. de Vries, I. Image_7_Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response.tif <p>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<sup>+</sup> 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<sup>+</sup> mDC. Inhibition of mitochondrial fragmentation or promotion of mitochondrial fusion impairs TLR-stimulation induced glycolysis and activation of CD1c<sup>+</sup> 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<sup>+</sup> mDCs. Our findings reveal that TLR stimulation differentially regulates mitochondrial dynamics in distinct human DC subsets, which contributes to their activation.</p> CD1c+ mDC;pDC;glutaminolysis;mitophagy;mitochondrial dynamics;OXPHOS;glycolysis 2018-11-01
    https://frontiersin.figshare.com/articles/figure/Image_7_Human_Dendritic_Cell_Subsets_Undergo_Distinct_Metabolic_Reprogramming_for_Immune_Response_tif/7283876
10.3389/fimmu.2018.02489.s007