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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.926220/full |
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| author | Sneha Muralidharan Sneha Muralidharan Federico Torta Federico Torta Michelle K. Lin Antoni Olona Marta Bagnati Aida Moreno-Moral Jeong-Hun Ko Shanshan Ji Bo Burla Markus R. Wenk Markus R. Wenk Hosana G. Rodrigues Enrico Petretto Enrico Petretto Enrico Petretto Jacques Behmoaras Jacques Behmoaras |
| author_facet | Sneha Muralidharan Sneha Muralidharan Federico Torta Federico Torta Michelle K. Lin Antoni Olona Marta Bagnati Aida Moreno-Moral Jeong-Hun Ko Shanshan Ji Bo Burla Markus R. Wenk Markus R. Wenk Hosana G. Rodrigues Enrico Petretto Enrico Petretto Enrico Petretto Jacques Behmoaras Jacques Behmoaras |
| author_sort | Sneha Muralidharan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:15:58Z |
| format | Article |
| id | doaj.art-a9de5caa16a34b808e70b7f8842cd4e3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T17:15:58Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a9de5caa16a34b808e70b7f8842cd4e32022-12-22T02:38:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.926220926220Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human MacrophagesSneha Muralidharan0Sneha Muralidharan1Federico Torta2Federico Torta3Michelle K. Lin4Antoni Olona5Marta Bagnati6Aida Moreno-Moral7Jeong-Hun Ko8Shanshan Ji9Bo Burla10Markus R. Wenk11Markus R. Wenk12Hosana G. Rodrigues13Enrico Petretto14Enrico Petretto15Enrico Petretto16Jacques Behmoaras17Jacques Behmoaras18Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, SingaporeInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, IndiaSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, SingaporePrecision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, SingaporeProgram in Cardiovascular and Metabolic Disorders (CVMD) and Center for Computational Biology (CCB), Duke NUS Graduate Medical School, Singapore, SingaporeDepartment of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United KingdomProgram in Cardiovascular and Metabolic Disorders (CVMD) and Center for Computational Biology (CCB), Duke NUS Graduate Medical School, Singapore, SingaporeDepartment of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United KingdomSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, SingaporePrecision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeLaboratory of Nutrients and Tissue Repair, School of Applied Sciences, University of Campinas, Limeira, BrazilProgram in Cardiovascular and Metabolic Disorders (CVMD) and Center for Computational Biology (CCB), Duke NUS Graduate Medical School, Singapore, SingaporeMRC London Institute of Medical Sciences (LMC), Imperial College, London, United KingdomInstitute for Big Data and Artificial Intelligence in Medicine, School of Science, China Pharmaceutical University, Nanjing, ChinaProgram in Cardiovascular and Metabolic Disorders (CVMD) and Center for Computational Biology (CCB), Duke NUS Graduate Medical School, Singapore, SingaporeDepartment of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United KingdomToll-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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.926220/fulllipidomicshuman macrophagestranscriptomicsglobosidesnetwork analysis |
| spellingShingle | Sneha Muralidharan Sneha Muralidharan Federico Torta Federico Torta Michelle K. Lin Antoni Olona Marta Bagnati Aida Moreno-Moral Jeong-Hun Ko Shanshan Ji Bo Burla Markus R. Wenk Markus R. Wenk Hosana G. Rodrigues Enrico Petretto Enrico Petretto Enrico Petretto Jacques Behmoaras Jacques Behmoaras Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages Frontiers in Immunology lipidomics human macrophages transcriptomics globosides network analysis |
| title | Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages |
| title_full | Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages |
| title_fullStr | Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages |
| title_full_unstemmed | Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages |
| title_short | Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages |
| title_sort | immunolipidomics reveals a globoside network during the resolution of pro inflammatory response in human macrophages |
| topic | lipidomics human macrophages transcriptomics globosides network analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.926220/full |
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