AUTHOR=Muralidharan Sneha , Torta Federico , Lin Michelle K. , Olona Antoni , Bagnati Marta , Moreno-Moral Aida , Ko Jeong-Hun , Ji Shanshan , Burla Bo , Wenk Markus R. , Rodrigues Hosana G. , Petretto Enrico , Behmoaras Jacques 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.926220

DOI=10.3389/fimmu.2022.926220

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>PDCD1</italic>, <italic>CD86</italic>, <italic>PTPRC</italic>, <italic>CD247</italic>, <italic>IFNG</italic>) and DC-SIGN signaling (<italic>RAF1</italic>, <italic>CD209</italic>), respectively. Our findings reveal Gb3 and Gb4 globosides as sphingolipids associated with the resolution phase of inflammatory response in human macrophages.</p>