Academic Journal
Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
| العنوان: | Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells |
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| المؤلفون: | Radomski, Nadine, Kägebein, Danny, Liebler-Tenorio, Elisabeth M., Karger, Axel, Rufer, Elke, Tews, Birke Andrea, Nagel, S., Einenkel, Rebekka, Müller, A., Rebbig, Annica, Knittler, Michael R. |
| سنة النشر: | 2017 |
| المجموعة: | OpenAgrar (Senat Bundesforschung, Bundesministeriums für Ernährung und Landwirtschaft) |
| مصطلحات موضوعية: | Text, article, ddc:570 |
| الوصف: | 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 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | Scientific Reports -- Sci Rep -- 2045-2322 -- 2615211-3 -- http://www.nature.com/srep/ -- http://www.bibliothek.uni-regensburg.de/ezeit/?2615211; https://doi.org/10.1038/s41598-017-04142-5; https://www.openagrar.de/receive/openagrar_mods_00027357; https://www.openagrar.de/servlets/MCRFileNodeServlet/openagrar_derivate_00003066/SD2017264.pdf; https://www.nature.com/articles/s41598-017-04142-5 |
| DOI: | 10.1038/s41598-017-04142-5 |
| الاتاحة: | https://doi.org/10.1038/s41598-017-04142-5 https://www.openagrar.de/receive/openagrar_mods_00027357 https://www.openagrar.de/servlets/MCRFileNodeServlet/openagrar_derivate_00003066/SD2017264.pdf https://www.nature.com/articles/s41598-017-04142-5 |
| Rights: | public ; https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2DDCBB93 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-017-04142-5 |
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