Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition.

Adrenal Cortex Hormones / pharmacology Dexamethasone / pharmacology Humans Mitochondrial Membranes / drug effects Mycobacterium tuberculosis / drug effects Phosphorylation / drug effects Receptors, Tumor Necrosis Factor, Type I / genetics Signal Transduction / genetics p38 Mitogen-Activated Protein Kinases / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
08 02 2019
Historique:
received: 07 05 2018
accepted: 09 01 2019
entrez: 10 2 2019
pubmed: 10 2 2019
medline: 9 4 2019
Statut: epublish

Résumé

Corticosteroids are host-directed drugs with proven beneficial effect on survival of tuberculosis (TB) patients, but their precise mechanisms of action in this disease remain largely unknown. Here we show that corticosteroids such as dexamethasone inhibit necrotic cell death of cells infected with Mycobacterium tuberculosis (Mtb) by facilitating mitogen-activated protein kinase phosphatase 1 (MKP-1)-dependent dephosphorylation of p38 MAPK. Characterization of infected mixed lineage kinase domain-like (MLKL) and tumor necrosis factor receptor 1 (TNFR1) knockout cells show that the underlying mechanism is independent from TNFα-signaling and necroptosis. Our results link corticosteroid function and p38 MAPK inhibition to abrogation of necrotic cell death mediated by mitochondrial membrane permeability transition, and open new avenues for research on novel host-directed therapies (HDT).

Identifiants

DOI: 10.1038/s41467-019-08405-9 PMID: 30737374 PMC: PMC6368550
pubmed: 30737374
doi: 10.1038/s41467-019-08405-9
pii: 10.1038/s41467-019-08405-9
pmc: PMC6368550
doi:

Substances chimiques

Adrenal Cortex Hormones 0
Receptors, Tumor Necrosis Factor, Type I 0
Dexamethasone 7S5I7G3JQL
p38 Mitogen-Activated Protein Kinases EC 2.7.11.24

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

688

Références

Cell Death Differ. 2018 May;25(5):951-965
pubmed: 29229989
Nat Rev Immunol. 2013 Sep;13(9):679-92
pubmed: 23954936
Nat Genet. 2005 Nov;37(11):1289-95
pubmed: 16200064
Cancer Res. 2000 May 1;60(9):2464-72
pubmed: 10811125
Virulence. 2017 Nov 17;8(8):1820-1832
pubmed: 28892415
Nat Rev Microbiol. 2015 Dec;13(12):741-8
pubmed: 26548915
J Infect Dis. 2017 Apr 1;215(7):1029-1039
pubmed: 28419315
EMBO J. 2014 Oct 1;33(19):2171-87
pubmed: 25056906
J Biol Chem. 2004 Sep 17;279(38):39846-55
pubmed: 15247300
Nat Rev Immunol. 2015 Apr;15(4):255-63
pubmed: 25765201
J Immunol. 2006 Apr 1;176(7):4267-74
pubmed: 16547264
Cell Death Dis. 2014 Jul 17;5:e1343
pubmed: 25032866
N Engl J Med. 2004 Oct 21;351(17):1741-51
pubmed: 15496623
Nat Rev Mol Cell Biol. 2014 Feb;15(2):135-47
pubmed: 24452471
Cell. 2012 Feb 3;148(3):434-46
pubmed: 22304914
FEBS J. 2013 Jan;280(2):489-504
pubmed: 22812510
J Biol Chem. 2011 Dec 2;286(48):41600-15
pubmed: 21862591
J Exp Med. 2005 Jan 17;201(2):279-89
pubmed: 15642743
PLoS Pathog. 2009 Oct;5(10):e1000645
pubmed: 19876393
Nat Rev Drug Discov. 2018 Jan;17(1):35-56
pubmed: 28935918
Nature. 2014 Sep 4;513(7516):90-4
pubmed: 25132550
Nucleic Acids Res. 2007;35(8):e63
pubmed: 17426130
Mol Cell Oncol. 2014 Oct 31;1(2):e955995
pubmed: 27308326
Nat Struct Biol. 2002 Apr;9(4):268-72
pubmed: 11896401
J Exp Med. 2006 Aug 7;203(8):1883-9
pubmed: 16880258
Nat Commun. 2015 Jul 09;6:7659
pubmed: 26158909
Cell. 2016 Jul 28;166(3):624-636
pubmed: 27374331
Open Forum Infect Dis. 2016 Sep 7;3(3):ofw151
pubmed: 27800526
Nat Commun. 2018 Jan 24;9(1):358
pubmed: 29367740
Nat Chem Biol. 2015 Oct;11(10):748-51
pubmed: 26379013
N Engl J Med. 2014 Jan 30;370(5):455-65
pubmed: 24476434
Cell Host Microbe. 2014 Oct 8;16(4):538-48
pubmed: 25299337
Mucosal Immunol. 2017 Nov;10(6):1553-1568
pubmed: 28401933
Sci Rep. 2015 Jun 24;5:11497
pubmed: 26105784
EMBO Rep. 2015 Jun;16(6):719-27
pubmed: 25825408
J Biol Chem. 1997 Sep 5;272(36):22776-80
pubmed: 9278438
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12420-5
pubmed: 14557547
J Exp Med. 1998 May 4;187(9):1477-85
pubmed: 9565639
Clin Infect Dis. 2005 Jul 15;41(2):201-8
pubmed: 15983916
Cell Death Differ. 2015 Feb;22(2):364
pubmed: 25578149
Cell. 2010 Mar 5;140(5):717-30
pubmed: 20211140
J Immunol. 2009 May 1;182(9):5865-72
pubmed: 19380835
Science. 2009 Jul 17;325(5938):332-6
pubmed: 19498109
Tuberculosis (Edinb). 2011 Jan;91(1):22-5
pubmed: 21112816
Biochim Biophys Acta. 2016 Oct;1863(10):2515-30
pubmed: 26902508
Cell. 2013 Apr 25;153(3):521-34
pubmed: 23582643
Cell Microbiol. 2007 Jun;9(6):1547-55
pubmed: 17298391
Cochrane Database Syst Rev. 2016 Apr 28;4:CD002244
pubmed: 27121755

Auteurs

Jessica Gräb (J)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.

Isabelle Suárez (I)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.

Edeltraud van Gumpel (E)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.

Sandra Winter (S)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.

Fynn Schreiber (F)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.

Anna Esser (A)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.

Christoph Hölscher (C)

German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
German Center for Infection Research (DZIF), Partner Site Hamburg - Lübeck - Borstel - Riems, 23845, Germany.

Melanie Fritsch (M)

Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.
Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.
Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, 50935, Cologne, Germany.

Marc Herb (M)

Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.
Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, 50935, Cologne, Germany.

Michael Schramm (M)

Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.
Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, 50935, Cologne, Germany.

Laurens Wachsmuth (L)

Institute for Genetics, University of Cologne, 50674, Cologne, Germany.

Christian Pallasch (C)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany.
Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.

Manolis Pasparakis (M)

Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.
Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.
Institute for Genetics, University of Cologne, 50674, Cologne, Germany.
ORCID: 0000-0002-9870-0966

Hamid Kashkar (H)

Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.
Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931, Cologne, Germany.
Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, 50935, Cologne, Germany.

Jan Rybniker (J)

Department I of Internal Medicine, University of Cologne, 50937, Cologne, Germany. jan.rybniker@uk-koeln.de.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany. jan.rybniker@uk-koeln.de.
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany. jan.rybniker@uk-koeln.de.

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Classifications MeSH

questionsmedicales.fr › Hormones corticosurrénaliennes › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Composés polycycliques › Composés à cycles fusionnés › Stéroïdes › Stéroïdes fluorés › Dexaméthasone › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Membranes intracellulaires › Membranes mitochondriales › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Métabolisme › Phosphorylation › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux facteurs de nécrose tumorale › Récepteur au facteur de nécrose tumorale de type I › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Corticosteroids inhibit Mycobacterium...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › p38 Mitogen-Activated Protein Kinases › Corticosteroids inhibit Mycobacterium...