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Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome

机译:Toll样受体诱导巨噬细胞的信号特异性重编程

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摘要

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.
机译:巨噬细胞响应于激活信号重新编程其脂质代谢。然而,缺乏缺乏对巨噬细胞脂质组的不同促炎刺激的系统级别了解。在这里,我们使用互补的“霰弹枪”和同位素示踪剂质谱方法来定义由各种收费的受体(TLR)和炎症细胞因子诱导的脂质生物合成,导入和组成的变化。“霰弹枪的脂质化数据显示出来这种不同的TLR和细胞因子诱导巨噬细胞获得不同的脂质体,表明它们在重塑脂质组合物中的特异性。机械研究表明,脂质组合物的差异重新编程由MyD88和Trif-干扰素信号传导途径的相反效应介导。最后,我们应用这些见解表明脂质组合物的扰动重新编程可以增强炎症并促进宿主防御对细菌挑战。这些研究提供了一种了解炎症刺激如何重新编程巨噬细胞的脂质组合,同时提供知识平台以利用差异脂多元族菌来影响免疫力的框架。

著录项

  • 来源
    《Cell metabolism》 |2020年第1期|共21页
  • 作者单位

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Mol &

    Med Pharmacol Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Med Div Dermatol Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Mol Biol Inst Los Angeles CA 90095 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Mayo Clin Dept Immunol Alix Sch Med Rochester MN 55905 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Mol &

    Med Pharmacol Los Angeles CA 90095 USA;

    Mayo Clin Dept Immunol Alix Sch Med Rochester MN 55905 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Univ Calif Los Angeles Dept Microbiol Immunol &

    Mol Genet Los Angeles CA 90095 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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