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Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome.
Hsieh, Wei-Yuan; Zhou, Quan D; York, Autumn G; Williams, Kevin J; Scumpia, Philip O; Kronenberger, Eliza B; Hoi, Xen Ping; Su, Baolong; Chi, Xun; Bui, Viet L; Khialeeva, Elvira; Kaplan, Amber; Son, Young Min; Divakaruni, Ajit S; Sun, Jie; Smale, Stephen T; Flavell, Richard A; Bensinger, Steven J.
Afiliação
  • Hsieh WY; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Zhou QD; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • York AG; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Immunobiology, Yale University S
  • Williams KJ; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Scumpia PO; Department of Medicine, Division of Dermatology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Kronenberger EB; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Hoi XP; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Su B; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Chi X; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Bui VL; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Khialeeva E; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kaplan A; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Son YM; Department of Immunology, Mayo Clinic Alix School of Medicine, Rochester, MN 55905, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic Alix School of Medicine, Rochester, MN 55905, USA.
  • Divakaruni AS; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Sun J; Department of Immunology, Mayo Clinic Alix School of Medicine, Rochester, MN 55905, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic Alix School of Medicine, Rochester, MN 55905, USA.
  • Smale ST; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
  • Bensinger SJ; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: sbensinger@mednet.ucla.edu
Cell Metab ; 32(1): 128-143.e5, 2020 07 07.
Article em En | MEDLINE | ID: mdl-32516576
ABSTRACT
Macrophages reprogram their lipid metabolism in response to activation signals. However, a systems-level understanding of how different pro-inflammatory stimuli reshape the macrophage lipidome is lacking. Here, we use complementary "shotgun" and isotope tracer mass spectrometry approaches to define the changes in lipid biosynthesis, import, and composition of macrophages induced by various Toll-like receptors (TLRs) and inflammatory cytokines. "Shotgun" lipidomics data revealed that different TLRs and cytokines induce macrophages to acquire distinct lipidomes, indicating their specificity in reshaping lipid composition. Mechanistic studies showed that differential reprogramming of lipid composition is mediated by the opposing effects of MyD88- and TRIF-interferon-signaling pathways. Finally, we applied these insights to show that perturbing reprogramming of lipid composition can enhance inflammation and promote host defense to bacterial challenge. These studies provide a framework for understanding how inflammatory stimuli reprogram lipid composition of macrophages while providing a knowledge platform to exploit differential lipidomics to influence immunity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Toll-Like / Lipidômica / Macrófagos Limite: Animals Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Toll-Like / Lipidômica / Macrófagos Limite: Animals Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos