Endogenous oxidized phospholipids reprogram cellular metabolism and boost hyperinflammation.

Alarmins / immunology Animals Cells, Cultured Disease Models, Animal Female Glycolysis / physiology Hypercholesterolemia / immunology Inflammation / prevention & control Lipopolysaccharides / immunology Macrophages / immunology Mice Mice, Inbred C57BL Mice, Knockout Oxidation-Reduction Oxidative Phosphorylation Pathogen-Associated Molecular Pattern Molecules / immunology Phosphatidylcholines / immunology Plaque, Atherosclerotic / pathology

Journal

Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354

Informations de publication

Date de publication:
01 2020
Historique:
received: 28 02 2019
accepted: 07 10 2019
pubmed: 27 11 2019
medline: 16 4 2020
entrez: 27 11 2019
Statut: ppublish

Résumé

Pathogen-associated molecular patterns (PAMPs) have the capacity to couple inflammatory gene expression to changes in macrophage metabolism, both of which influence subsequent inflammatory activities. Similar to their microbial counterparts, several self-encoded damage-associated molecular patterns (DAMPs) induce inflammatory gene expression. However, whether this symmetry in host responses between PAMPs and DAMPs extends to metabolic shifts is unclear. Here, we report that the self-encoded oxidized phospholipid oxPAPC alters the metabolism of macrophages exposed to lipopolysaccharide. While cells activated by lipopolysaccharide rely exclusively on glycolysis, macrophages exposed to oxPAPC also use mitochondrial respiration, feed the Krebs cycle with glutamine, and favor the accumulation of oxaloacetate in the cytoplasm. This metabolite potentiates interleukin-1β production, resulting in hyperinflammation. Similar metabolic adaptions occur in vivo in hypercholesterolemic mice and human subjects. Drugs that interfere with oxPAPC-driven metabolic changes reduce atherosclerotic plaque formation in mice, thereby underscoring the importance of DAMP-mediated activities in pathophysiological conditions.

Identifiants

DOI: 10.1038/s41590-019-0539-2 PMID: 31768073 PMC: PMC6923570
pubmed: 31768073
doi: 10.1038/s41590-019-0539-2
pii: 10.1038/s41590-019-0539-2
pmc: PMC6923570
mid: NIHMS1541070
doi:

Substances chimiques

Alarmins 0
Lipopolysaccharides 0
Pathogen-Associated Molecular Pattern Molecules 0
Phosphatidylcholines 0
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

42-53

Subventions

Organisme : NHLBI NIH HHS
ID : HHSN268201500001C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121066
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034854
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500001I
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115217
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC25195
Pays : United States
Organisme : NHLBI NIH HHS
ID : R15 HL121770
Pays : United States
Organisme : NHLBI NIH HHS
ID : K99 HL136875
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

Marco Di Gioia (M)

Division of Immunology and Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Roberto Spreafico (R)

Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0001-8282-7658

James R Springstead (JR)

Department of Chemical and Paper Engineering, Western Michigan University, Kalamazoo, MI, USA.

Michael M Mendelson (MM)

Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
ORCID: 0000-0001-7590-3958

Roby Joehanes (R)

Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Daniel Levy (D)

Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Ivan Zanoni (I)

Division of Immunology and Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. ivan.zanoni@childrens.harvard.edu.
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy. ivan.zanoni@childrens.harvard.edu.
ORCID: 0000-0002-3423-7474

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Alarmines › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Eucaryotes › Animaux › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Cellules › Cellules cultivées › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme lipidique › Dyslipidémies › Hyperlipidémies › Hypercholestérolémie › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Métabolisme › Métabolisme énergétique › Oxydoréduction › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Métabolisme › Phosphorylation › Phosphorylation oxydative › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Facteurs biologiques › Molécules contenant des motifs associés aux pathogènes › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › Lipides › Lipides membranaires › Phospholipides › Glycérophosphate › Acides phosphatidiques › Glycérophospholipides › Phosphatidylcholines › Endogenous oxidized phospholipids reprogram...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Plaque d'athérosclérose › Endogenous oxidized phospholipids reprogram...