Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages

Frontiers in Immunology

Jeong-Hun Ko¹  Jacques Behmoaras¹  Marta Bagnati¹  Enrico Petretto²  Sneha Muralidharan³  Hosana G. Rodrigues⁴  Markus R. Wenk⁶  Federico Torta⁶  Antoni Olona⁷  Aida Moreno-Moral⁷  Michelle K. Lin⁸  Shanshan Ji⁸  Bo Burla⁸ 

[1]Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom

[2]Institute for Big Data and Artificial Intelligence in Medicine, School of Science, China Pharmaceutical University, Nanjing, China

[3]Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, India

[4]Laboratory of Nutrients and Tissue Repair, School of Applied Sciences, University of Campinas, Limeira, Brazil

[5]MRC London Institute of Medical Sciences (LMC), Imperial College, London, United Kingdom

[6]Precision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

[7]Program in Cardiovascular and Metabolic Disorders (CVMD) and Center for Computational Biology (CCB), Duke NUS Graduate Medical School, Singapore, Singapore

[8]Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore

关键词: lipidomics;    human macrophages;    transcriptomics;    globosides;    network analysis;   

DOI  :  10.3389/fimmu.2022.926220

来源: DOAJ

【 摘 要 】

Toll-like receptor 4 (TLR4)-mediated changes in macrophages reshape intracellular lipid pools to coordinate an effective innate immune response. Although this has been previously well-studied in different model systems, it remains incompletely understood in primary human macrophages. Here we report time-dependent lipidomic and transcriptomic responses to lipopolysaccharide (LPS) in primary human macrophages from healthy donors. We grouped the variation of ~200 individual lipid species measured by LC-MS/MS into eight temporal clusters. Among all other lipids, glycosphingolipids (glycoSP) and cholesteryl esters (CE) showed a sharp increase during the resolution phase (between 8h or 16h post LPS). GlycoSP, belonging to the globoside family (Gb3 and Gb4), showed the greatest inter-individual variability among all lipids quantified. Integrative network analysis between GlycoSP/CE levels and genome-wide transcripts, identified Gb4 d18:1/16:0 and CE 20:4 association with subnetworks enriched for T cell receptor signaling (PDCD1, CD86, PTPRC, CD247, IFNG) and DC-SIGN signaling (RAF1, CD209), respectively. Our findings reveal Gb3 and Gb4 globosides as sphingolipids associated with the resolution phase of inflammatory response in human macrophages.

【 授权许可】

Unknown