biostudies-literatureUnknown7(1)Radomski NChlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival. Tubulin deacetylase/autophagy regulator HDAC6 associates with disintegrated inclusions, thereby further disrupting their subcellular localisation and stability. Bacterial remnants are decorated with defScientific reports3923https://www.ebi.ac.uk/biostudies/studies/S-EPMC5478671biostudies-literatureMito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells.PMC5478671Karger ATews BARebbig AMuller ARufer ERadomski NKnittler MRNagel SKagebein DLiebler-Tenorio EEinenkel RfalseMito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells.Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival. Tubulin deacetylase/autophagy regulator HDAC6 associates with disintegrated inclusions, thereby further disrupting their subcellular localisation and stability. Bacterial remnants are decorated with def2017-01-01T00:00:00Z2017 Jun2026-05-05T09:46:38.201Z2019-03-27T02:48:07ZS-EPMC54786712863438810.1038/s41598-017-04142-5