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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-\u03b1 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 defective mitochondria, mito-aggresomal structures, and components of the ubiquitin\/autophagy machinery before they are degraded via mito-xenophagy. The mechanism depends on cytoprotective HSP25\/27, the E3 ubiquitin ligase Parkin and HDAC6 and promotes chlamydial antigen generation for presentation on MHC I. We propose that this novel mito-xenophagic pathway linking innate and adaptive immunity is critical for effective DC-mediated anti-bacterial resistance.<\/jats:p>","DOI":"10.1038\/s41598-017-04142-5","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T14:52:04Z","timestamp":1497451924000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Nadine","family":"Radomski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"K\u00e4gebein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Liebler-Tenorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Karger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Rufer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birke Andrea","family":"Tews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Nagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekka","family":"Einenkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annica","family":"Rebbig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Knittler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,20]]},"reference":[{"key":"4142_CR1","doi-asserted-by":"publisher","first-page":"3920","DOI":"10.1002\/1873-3468.12295","volume":"55","author":"N Radomski","year":"2016","unstructured":"Radomski, N., Einenkel, R., M\u00fcller, A. & Knittler, M. 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