Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages.
Title | Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Muralidharan S, Torta F, Lin MK, Olona A, Bagnati M, Moreno-Moral A, Ko J-H, Ji S, Burla B, Wenk MR, Rodrigues HG, Petretto E, Behmoaras J |
Journal | Front Immunol |
Volume | 13 |
Pagination | 926220 |
Date Published | 2022 |
ISSN | 1664-3224 |
Keywords | Chromatography, Liquid, Globosides, Humans, Lipopolysaccharides, Macrophages, Tandem Mass Spectrometry |
Abstract | 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 (, , , , ) and DC-SIGN signaling (, ), respectively. Our findings reveal Gb3 and Gb4 globosides as sphingolipids associated with the resolution phase of inflammatory response in human macrophages. |
DOI | 10.3389/fimmu.2022.926220 |
Alternate Journal | Front Immunol |
PubMed ID | 35844525 |
PubMed Central ID | PMC9280915 |
Grant List | MR/M004716/1 / MRC_ / Medical Research Council / United Kingdom MR/N01121X/1 / MRC_ / Medical Research Council / United Kingdom |