PMID- 28634388
OWN - NLM
STAT- MEDLINE
DCOM- 20190111
LR  - 20191210
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jun 20
TI  - Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in 
      dendritic cells.
PG  - 3923
LID - 10.1038/s41598-017-04142-5 [doi]
LID - 3923
AB  - 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-alpha 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.
FAU - Radomski, Nadine
AU  - Radomski N
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Sudufer 10, D-17493, Greifswald, Isle of Riems, Germany.
FAU - Kagebein, Danny
AU  - Kagebein D
AD  - German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120, 
      Heidelberg, Germany.
FAU - Liebler-Tenorio, Elisabeth
AU  - Liebler-Tenorio E
AD  - Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal 
      Research Institute of Animal Health, Naumburger Strasse 96a, D-07743, Jena, 
      Germany.
FAU - Karger, Axel
AU  - Karger A
AD  - Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 
      Federal Research Institute of Animal Health, Sudufer 10, D-17493, Greifswald, 
      Isle of Riems, Germany.
FAU - Rufer, Elke
AU  - Rufer E
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Sudufer 10, D-17493, Greifswald, Isle of Riems, Germany.
FAU - Tews, Birke Andrea
AU  - Tews BA
AD  - Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 
      Federal Research Institute of Animal Health, Sudufer 10, D-17493, Greifswald, 
      Isle of Riems, Germany.
FAU - Nagel, Stefanie
AU  - Nagel S
AD  - German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120, 
      Heidelberg, Germany.
FAU - Einenkel, Rebekka
AU  - Einenkel R
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Sudufer 10, D-17493, Greifswald, Isle of Riems, Germany.
FAU - Muller, Anne
AU  - Muller A
AD  - University of Tubingen, Interfaculty Institute of Biochemistry, 
      Hoppe-Seyler-Strasse 4, D-72076, Tubingen, Germany.
FAU - Rebbig, Annica
AU  - Rebbig A
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Sudufer 10, D-17493, Greifswald, Isle of Riems, Germany.
FAU - Knittler, Michael R
AU  - Knittler MR
AD  - Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute 
      of Animal Health, Sudufer 10, D-17493, Greifswald, Isle of Riems, Germany. 
      michael.knittler@fli.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170620
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.1.1.4 (Phospholipases A2, Cytosolic)
RN  - EC 3.5.1.98 (Histone Deacetylase 6)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/*metabolism
MH  - Cell Line
MH  - Chlamydia/cytology/*growth & development
MH  - Coculture Techniques
MH  - Dendritic Cells/*cytology/metabolism/microbiology
MH  - Glycolysis
MH  - Histone Deacetylase 6/metabolism
MH  - Mice
MH  - Microbial Viability
MH  - *Mitophagy
MH  - Phospholipases A2, Cytosolic/*metabolism
MH  - T-Lymphocytes/cytology/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC5478671
COIS- The authors declare that they have no competing interests.
EDAT- 2017/06/22 06:00
MHDA- 2019/01/12 06:00
PMCR- 2017/06/20
CRDT- 2017/06/22 06:00
PHST- 2017/01/12 00:00 [received]
PHST- 2017/05/10 00:00 [accepted]
PHST- 2017/06/22 06:00 [entrez]
PHST- 2017/06/22 06:00 [pubmed]
PHST- 2019/01/12 06:00 [medline]
PHST- 2017/06/20 00:00 [pmc-release]
AID - 10.1038/s41598-017-04142-5 [pii]
AID - 4142 [pii]
AID - 10.1038/s41598-017-04142-5 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jun 20;7(1):3923. doi: 10.1038/s41598-017-04142-5.