IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46068-3.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46068-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46068-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    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. "Author Correction: Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution," Nature, Nature, vol. 568(7751), pages 4-4, April.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jarne Beliën & Stijn Swinnen & Robbe D’hondt & Laia Verdú de Juan & Nina Dedoncker & Patrick Matthys & Jan Bauer & Celine Vens & Sinéad Moylett & Bénédicte Dubois, 2024. "CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Rasmus Berglund & Yufei Cheng & Eliane Piket & Milena Z. Adzemovic & Manuel Zeitelhofer & Tomas Olsson & Andre Ortlieb Guerreiro-Cacais & Maja Jagodic, 2024. "The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Zu-Qiang Liu & Hao Dai & Lu Yao & Wei-Feng Chen & Yun Wang & Li-Yun Ma & Xiao-Qing Li & Sheng-Li Lin & Meng-Jiang He & Ping-Ting Gao & Xin-Yang Liu & Jia-Xin Xu & Xiao-Yue Xu & Ke-Hao Wang & Li Wang &, 2023. "A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Thanh Loc Nguyen & Youngjin Choi & Jihye Im & Hyunsu Shin & Ngoc Man Phan & Min Kyung Kim & Seung Woo Choi & Jaeyun Kim, 2022. "Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Florian Pernin & Qiao-Ling Cui & Abdulshakour Mohammadnia & Milton G. F. Fernandes & Jeffery A. Hall & Myriam Srour & Roy W. R. Dudley & Stephanie E. J. Zandee & Wendy Klement & Alexandre Prat & Hanna, 2024. "Regulation of stress granule formation in human oligodendrocytes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Noah R. Johnson & Peng Yuan & Erika Castillo & T. Peter Lopez & Weizhou Yue & Annalise Bond & Brianna M. Rivera & Miranda C. Sullivan & Masakazu Hirouchi & Kurt Giles & Atsushi Aoyagi & Carlo Condello, 2023. "CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    7. Janos Groh & Tassnim Abdelwahab & Yogita Kattimani & Michaela Hörner & Silke Loserth & Viktoria Gudi & Robert Adalbert & Fabian Imdahl & Antoine-Emmanuel Saliba & Michael Coleman & Martin Stangel & Mi, 2023. "Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Suvra Nath & Jose C. Martínez Santamaría & Yu-Hsuan Chu & James S. Choi & Pasquale Conforti & Jia-Di Lin & Roman Sankowski & Lukas Amann & Christos Galanis & Kexin Wu & Sachin S. Deshpande & Andreas V, 2024. "Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    9. Shannon Tansley & Sonali Uttam & Alba Ureña Guzmán & Moein Yaqubi & Alain Pacis & Marc Parisien & Haley Deamond & Calvin Wong & Oded Rabau & Nicole Brown & Lisbet Haglund & Jean Ouellet & Carlo Santag, 2022. "Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Duy Pham & Xiao Tan & Brad Balderson & Jun Xu & Laura F. Grice & Sohye Yoon & Emily F. Willis & Minh Tran & Pui Yeng Lam & Arti Raghubar & Priyakshi Kalita-de Croft & Sunil Lakhani & Jana Vukovic & Ma, 2023. "Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    11. Daniel Bormann & Michael Knoflach & Emilia Poreba & Christian J. Riedl & Giulia Testa & Cyrille Orset & Anthony Levilly & Andréa Cottereau & Philipp Jauk & Simon Hametner & Nadine Stranzl & Bahar Gola, 2024. "Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    12. Tian Zhou & Yuxin Li & Xiaoyu Li & Fanzhuo Zeng & Yanxia Rao & Yang He & Yafei Wang & Meizhen Liu & Dali Li & Zhen Xu & Xin Zhou & Siling Du & Fugui Niu & Jiyun Peng & Xifan Mei & Sheng-Jian Ji & Yous, 2022. "Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    13. Moumita Datta & Stefanie M. Hansen & Ori Staszewski, 2020. "Microglial Expression of Hdac1 and Hdac2 is Dispensable for Experimental Autoimmune Encephalomyelitis (EAE) Progression," J, MDPI, vol. 3(4), pages 1-8, October.
    14. Qianqian Zhang & Sijin Cheng & Yongzhi Wang & Mengdi Wang & Yufeng Lu & Zengqi Wen & Yuxin Ge & Qiang Ma & Youqiao Chen & Yaowu Zhang & Ren Cao & Min Li & Weihao Liu & Bo Wang & Qian Wu & Wenqing Jia , 2021. "Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    15. Jake R. Thomas & Anna Appios & Emily F. Calderbank & Nagisa Yoshida & Xiaohui Zhao & Russell S. Hamilton & Ashley Moffett & Andrew Sharkey & Elisa Laurenti & Courtney W. Hanna & Naomi McGovern, 2023. "Primitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Nourhan Abdelfattah & Parveen Kumar & Caiyi Wang & Jia-Shiun Leu & William F. Flynn & Ruli Gao & David S. Baskin & Kumar Pichumani & Omkar B. Ijare & Stephanie L. Wood & Suzanne Z. Powell & David L. H, 2022. "Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Peter Androvic & Martina Schifferer & Katrin Perez Anderson & Ludovico Cantuti-Castelvetri & Hanyi Jiang & Hao Ji & Lu Liu & Garyfallia Gouna & Stefan A. Berghoff & Simon Besson-Girard & Johanna Knofe, 2023. "Spatial Transcriptomics-correlated Electron Microscopy maps transcriptional and ultrastructural responses to brain injury," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    18. Daniela Rodrigues-Amorim & P. Lorenzo Bozzelli & TaeHyun Kim & Liwang Liu & Oliver Gibson & Cheng-Yi Yang & Mitchell H. Murdock & Fabiola Galiana-Melendez & Brooke Schatz & Alexis Davison & Md Rezaul , 2024. "Multisensory gamma stimulation mitigates the effects of demyelination induced by cuprizone in male mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    19. Erik Nutma & Nurun Fancy & Maria Weinert & Stergios Tsartsalis & Manuel C. Marzin & Robert C. J. Muirhead & Irene Falk & Marjolein Breur & Joy Bruin & David Hollaus & Robin Pieterman & Jasper Anink & , 2023. "Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    20. Haven Tillmon & Breeanne M. Soteros & Liang Shen & Qifei Cong & Mackenna Wollet & Julianne General & Hanna Chin & John Beichen Lee & Flavia R. Carreno & David A. Morilak & Jun Hee Kim & Gek Ming Sia, 2024. "Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46068-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.