Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome
| Autor: | Wei Yuan Hsieh, Xen Ping Hoi, Viet L. Bui, Elvira Khialeeva, Xun Chi, Autumn G. York, Young Min Son, Amber Kaplan, Ajit S. Divakaruni, Jie Sun, Richard A. Flavell, Quan D. Zhou, Eliza B. Kronenberger, Stephen T. Smale, Philip O. Scumpia, Kevin J. Williams, Baolong Su, Steven J. Bensinger |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Physiology Knockout stable isotope tracer analysis Inflammation Mice Transgenic Medical Biochemistry and Metabolomics Article Transgenic Proinflammatory cytokine Cell Line 03 medical and health sciences Mice Endocrinology & Metabolism 0302 clinical medicine Lipid biosynthesis Lipidomics medicine Macrophage Animals 2.1 Biological and endogenous factors Aetiology stearoyl-CoA desaturase Molecular Biology Mice Knockout Chemistry Macrophages Inflammatory and immune system Toll-Like Receptors Lipid metabolism Cell Biology interferon Lipidome MyD88 acetylated-LDL Cell biology 030104 developmental biology Infectious Diseases host defense inflammation Biochemistry and Cell Biology medicine.symptom Reprogramming 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cell metabolism, vol 32, iss 1 Cell Metab |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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