Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells

Abstract 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...

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Autores principales:	Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R. Knittler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c701232460348eeb4e19469f802be3d
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spelling	oai:doaj.org-article:9c701232460348eeb4e19469f802be3d2021-12-02T12:30:36ZMito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells10.1038/s41598-017-04142-52045-2322https://doaj.org/article/9c701232460348eeb4e19469f802be3d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04142-5https://doaj.org/toc/2045-2322Abstract 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.Nadine RadomskiDanny KägebeinElisabeth Liebler-TenorioAxel KargerElke RuferBirke Andrea TewsStefanie NagelRebekka EinenkelAnne MüllerAnnica RebbigMichael R. KnittlerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadine Radomski Danny Kägebein Elisabeth Liebler-Tenorio Axel Karger Elke Rufer Birke Andrea Tews Stefanie Nagel Rebekka Einenkel Anne Müller Annica Rebbig Michael R. Knittler Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
description	Abstract 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.
format	article
author	Nadine Radomski Danny Kägebein Elisabeth Liebler-Tenorio Axel Karger Elke Rufer Birke Andrea Tews Stefanie Nagel Rebekka Einenkel Anne Müller Annica Rebbig Michael R. Knittler
author_facet	Nadine Radomski Danny Kägebein Elisabeth Liebler-Tenorio Axel Karger Elke Rufer Birke Andrea Tews Stefanie Nagel Rebekka Einenkel Anne Müller Annica Rebbig Michael R. Knittler
author_sort	Nadine Radomski
title	Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
title_short	Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
title_full	Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
title_fullStr	Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
title_full_unstemmed	Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
title_sort	mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9c701232460348eeb4e19469f802be3d
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Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells

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