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

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...

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Bibliographic Details
Published in:Frontiers in immunology 2022-06, Vol.13, p.926220-926220
Main Authors: 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
Format: Article
Language:English
Subjects:
Chromatography, Liquid
Globosides
human macrophages
Humans
Immunology
lipidomics
Lipopolysaccharides
Macrophages - immunology
network analysis
Tandem Mass Spectrometry
transcriptomics
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.926220