TitleImmunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages.
Publication TypeJournal Article
Year of Publication2022
AuthorsMuralidharan 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
JournalFront Immunol
Date Published2022
KeywordsChromatography, Liquid, Globosides, Humans, Lipopolysaccharides, Macrophages, Tandem Mass Spectrometry

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.

Alternate JournalFront Immunol
PubMed ID35844525
PubMed Central IDPMC9280915
Grant ListMR/M004716/1 / MRC_ / Medical Research Council / United Kingdom
MR/N01121X/1 / MRC_ / Medical Research Council / United Kingdom