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

Aletta M R van den Bosch, Marlijn van der Poel, Nina L Fransen, Maria C J Vincenten, Anneleen M Bobeldijk, Aldo Jongejan, Hendrik J Engelenburg, Perry D Moerland, Joost Smolders, Inge Huitinga, Jörg Hamann

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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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.

Original languageEnglish
Pages (from-to)1667
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 23 Feb 2024

Keywords

  • Humans
  • Multiple Sclerosis/pathology
  • Microglia/metabolism
  • Nervous System Diseases/pathology
  • Stroke/pathology
  • Cytokines/metabolism
  • Immunoglobulins/metabolism

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