The 853rd MIB Seminar
(Joint Usage/Research Center for the Multi-stratified Host Defense System)
Title
The myeloid side of the brain
Speaker
Prof. Marco Prinz, M.D., Ph.D.
Professor
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Germany
Date
May 9 (Fri), 2025
16:00-17:00
Venue
Lecture Room 102, 1F, Biomedical Research Station, Hospital Campus
No.34 on the following linked map.
Campus Map
Abstract
As tissue resident macrophages of the central nervous system (CNS) parenchyma, microglia perform diverse essential functions during homeostasis and perturbations. They primarily interact with neurons via synaptic engulfment and through the rapid elimination of apoptotic cells and nonfunctional synapses. Here, by combining unbiased lipidomics and high resolution spatial lipid imaging, deep single-cell transcriptome analysis and novel cell type-specific mutants, we identified a previously unknown mode of microglial interaction with neurons. During homeostasis, microglia deliver the lysosomal enzyme b-hexosaminidase to neurons for the degradation of the ganglioside GM2 that is integral to maintaining cell membrane organization and function. Absence of Hexb, encoding the β subunit of b-hexosaminidase, in both mice and patients suffering from neurodegenerative Sandhoff disease leads to a massive accumulation of GM2 derivatives in a characteristic spatiotemporal manner. In mice, neuronal GM2 gangliosides subsequently engage the macrophage galactose-type lectin (MGL)2 receptor on microglia via N-acetylgalactosamine (GalNAc) residues, leading to lethal neurodegeneration. Notably, microglial replacement is able to break this degenerative cycle and fully restore CNS homeostasis.
Major Publications
- Amann L et al. Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages, Science Immunology 9(102), 2024.
- Vinnakota JM et al. Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome, Nature Cancer 5(8), 2024.
- Sankowski R et al. Multiomic spatial landscape of innate immune cells at human central nervous system borders, Nature Medicine 30(1), 2024.
- Amann L et al. Mechanisms of myeloid cell entry to the healthy and diseased central nervous system, Nature Immunology 24(3), 2023.
- Masuda T et al. Specification of CNS macrophage subsets occurs postnatally in defined niches, Nature 604(7907), 2022.
Contact
Division of Molecular Neuroimmunology, Medical Institute of Bioregulation
Takahiro Masuda
TEL: 092 (642) 6800
E-mail: takahiro.masuda[＠]bioreg.kyushu-u.ac.jp
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