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Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation

Author

Listed:
  • Aletta M. R. Bosch

    (Netherlands Institute for Neuroscience)

  • Marlijn Poel

    (Netherlands Institute for Neuroscience)

  • Nina L. Fransen

    (Netherlands Institute for Neuroscience)

  • Maria C. J. Vincenten

    (Netherlands Institute for Neuroscience)

  • Anneleen M. Bobeldijk

    (Netherlands Institute for Neuroscience)

  • Aldo Jongejan

    (Amsterdam University Medical Center)

  • Hendrik J. Engelenburg

    (Netherlands Institute for Neuroscience)

  • Perry D. Moerland

    (Amsterdam University Medical Center)

  • Joost Smolders

    (Netherlands Institute for Neuroscience
    Erasmus Medical Center)

  • Inge Huitinga

    (Netherlands Institute for Neuroscience
    University of Amsterdam)

  • Jörg Hamann

    (Netherlands Institute for Neuroscience
    Amsterdam University Medical Center)

Abstract

Microglia nodules (HLA-DR+ cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia nodules are associated with more severe MS pathology. Compared to microglia nodules in stroke, those in MS show enhanced expression of genes previously found upregulated in MS lesions. Furthermore, genes associated with lipid metabolism, presence of T and B cells, production of immunoglobulins and cytokines, activation of the complement cascade, and metabolic stress are upregulated in microglia nodules in MS. Compared to stroke, they more frequently phagocytose oxidized phospholipids and possess a more tubular mitochondrial network. Strikingly, in MS, some microglia nodules encapsulate partially demyelinated axons. Taken together, we propose that activation of microglia nodules in MS by cytokines and immunoglobulins, together with phagocytosis of oxidized phospholipids, may lead to a microglia phenotype prone to MS lesion formation.

Suggested Citation

  • Aletta M. R. Bosch & Marlijn Poel & Nina L. Fransen & Maria C. J. Vincenten & Anneleen M. Bobeldijk & Aldo Jongejan & Hendrik J. Engelenburg & Perry D. Moerland & Joost Smolders & Inge Huitinga & Jörg, 2024. "Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46068-3
    DOI: 10.1038/s41467-024-46068-3
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    1. Martina Absinta & Dragan Maric & Marjan Gharagozloo & Thomas Garton & Matthew D. Smith & Jing Jin & Kathryn C. Fitzgerald & Anya Song & Poching Liu & Jing-Ping Lin & Tianxia Wu & Kory R. Johnson & Dor, 2021. "A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis," Nature, Nature, vol. 597(7878), pages 709-714, September.
    2. Lucas Schirmer & Dmitry Velmeshev & Staffan Holmqvist & Max Kaufmann & Sebastian Werneburg & Diane Jung & Stephanie Vistnes & John H. Stockley & Adam Young & Maike Steindel & Brian Tung & Nitasha Goya, 2019. "Neuronal vulnerability and multilineage diversity in multiple sclerosis," Nature, Nature, vol. 573(7772), pages 75-82, September.
    3. Takahiro Masuda & Roman Sankowski & Ori Staszewski & Chotima Böttcher & Lukas Amann & Sagar & Christian Scheiwe & Stefan Nessler & Patrik Kunz & Geert Loo & Volker Arnd Coenen & Peter Christoph Reinac, 2019. "Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution," Nature, Nature, vol. 566(7744), pages 388-392, February.
    4. Simone Bido & Sharon Muggeo & Luca Massimino & Matteo Jacopo Marzi & Serena Gea Giannelli & Elena Melacini & Melania Nannoni & Diana Gambarè & Edoardo Bellini & Gabriele Ordazzo & Greta Rossi & Camill, 2021. "Author Correction: Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
    5. Takahiro Masuda & Roman Sankowski & Ori Staszewski & Chotima Böttcher & Lukas Amann & Sagar & Christian Scheiwe & Stefan Nessler & Patrik Kunz & Geert Loo & Volker Arnd Coenen & Peter Christoph Reinac, 2019. "Author Correction: Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution," Nature, Nature, vol. 568(7751), pages 4-4, April.
    6. Ellis Patrick & Mariko Taga & Ayla Ergun & Bernard Ng & William Casazza & Maria Cimpean & Christina Yung & Julie A Schneider & David A Bennett & Chris Gaiteri & Philip L De Jager & Elizabeth M Bradsha, 2020. "Deconvolving the contributions of cell-type heterogeneity on cortical gene expression," PLOS Computational Biology, Public Library of Science, vol. 16(8), pages 1-17, August.
    7. Simone Bido & Sharon Muggeo & Luca Massimino & Matteo Jacopo Marzi & Serena Gea Giannelli & Elena Melacini & Melania Nannoni & Diana Gambarè & Edoardo Bellini & Gabriele Ordazzo & Greta Rossi & Camill, 2021. "Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    8. Marlijn Poel & Thomas Ulas & Mark R. Mizee & Cheng-Chih Hsiao & Suzanne S. M. Miedema & Adelia & Karianne G. Schuurman & Boy Helder & Sander W. Tas & Joachim L. Schultze & Jörg Hamann & Inge Huitinga, 2019. "Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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