@article{3aa5485d5edc43ea90e32e6f9ce43e5a,
title = "Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome",
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.",
keywords = "MyD88, acetylated-LDL, host defense, inflammation, interferon, lipidomics, macrophages, stable isotope tracer analysis, stearoyl-CoA desaturase, toll-like receptors",
author = "Hsieh, {Wei Yuan} and Zhou, {Quan D.} and York, {Autumn G.} and Williams, {Kevin J.} and Scumpia, {Philip O.} and Kronenberger, {Eliza B.} and Hoi, {Xen Ping} and Baolong Su and Xun Chi and Bui, {Viet L.} and Elvira Khialeeva and Amber Kaplan and Son, {Young Min} and Divakaruni, {Ajit S.} and Jie Sun and Smale, {Stephen T.} and Flavell, {Richard A.} and Bensinger, {Steven J.}",
note = "Funding Information: These data are available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench ( https://www.metabolomicsworkbench.org ) where it has been assigned Project ID: PR000914. The data can be accessed directly via the Project DOI: https://doi.org/10.21228/M8JH69 . This work is supported by NIH grant U2C-DK119886. Funding Information: A.G.Y. was supported in part by California HIV/AIDS Research Program training fellowship (D12-LA-351), and is currently supported by the Howard Hughes Medical Institute Hanna H. Gray Fellowship; S.J.B. was supported by NIH AI093768 , AI122282 , and HL146358 ; P.O.S. was supported by NIH AR066545 and AR073940 ; J.S. was supported by NIH AG047156 and HL126647 . The research described was also supported by NIH/ National Center for Advancing Translational Sciences (NCATS) UCLA CTSI grant Number UL1TR001881 . Funding Information: A.G.Y. was supported in part by California HIV/AIDS Research Program training fellowship (D12-LA-351), and is currently supported by the Howard Hughes Medical Institute Hanna H. Gray Fellowship; S.J.B. was supported by NIH AI093768, AI122282, and HL146358; P.O.S. was supported by NIH AR066545 and AR073940; J.S. was supported by NIH AG047156 and HL126647. The research described was also supported by NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI grant Number UL1TR001881. W.Y.H. Q.Z. and A.G.Y. conceptualized, designed and/or implemented experiments, analyzed data, and constructed the manuscript; K.J.W. P.O.S. V.L.B. E.K. X.P.H, X.C. A.Z. A.K. and A.S.D. designed, implemented experiments, and analyzed data; L.K. D.Q. B.L.S. and K.J.W. provided lipidomics and computational analysis; S.T.S. and R.A.F. provided resources and supervision, contributed to conceptualization, and revision of the manuscript; S.J.B. provided resources and supervision, and contributed to conceptualization, designed experiments, analyzed data, and construction of the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = jul,
day = "7",
doi = "10.1016/j.cmet.2020.05.003",
language = "English (US)",
volume = "32",
pages = "128--143.e5",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}