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Updated: Oct 17, 2025
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis
Roman Sankowski1,2, Jasmin Ahmari1, Charlotte Mezö1,3
1Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Abstract:
The immune cells of the central nervous system (CNS) comprise parenchymal microglia and at the CNS border regions meningeal, perivascular, and choroid plexus macrophages (collectively called CNS-associated macrophages, CAMs). While previous work has shown that microglial properties depend on environmental signals from the commensal microbiota, the effects of microbiota on CAMs are unknown. By combining several microbiota manipulation approaches, genetic mouse models, and single-cell RNA-sequencing, we have characterized CNS myeloid cell composition and function. Under steady-state conditions, the transcriptional profiles and numbers of choroid plexus macrophages were found to be tightly regulated by complex microbiota. In contrast, perivascular and meningeal macrophages were affected to a lesser extent. An acute perturbation through viral infection evoked an attenuated immune response of all CAMs in germ-free mice. We further assessed CAMs in a more chronic pathological state in 5xFAD mice, a model for Alzheimer's disease, and found enhanced amyloid beta uptake exclusively by perivascular macrophages in germ-free 5xFAD mice. Our results aid the understanding of distinct microbiota-CNS macrophage interactions during homeostasis and disease, which could potentially be targeted therapeutically.
Insights
The gut microbiota significantly influences central nervous system (CNS)-associated macrophages (CAMs), impacting their numbers and function during homeostasis and disease. Germ-free conditions alter immune responses and amyloid-beta uptake in Alzheimer's models.
Area of Science:
- Neuroimmunology
- Microbiome research
- Cellular and Molecular Neuroscience
Background:
- Central nervous system (CNS) immunity involves microglia and CNS-associated macrophages (CAMs).
- Microglia function is known to be modulated by gut microbiota.
- The impact of microbiota on CAMs remains largely unexplored.
Purpose of the Study:
- To investigate the influence of gut microbiota on the composition and function of CNS-associated macrophages (CAMs).
- To characterize microbiota-CAM interactions in both homeostatic and disease conditions.
Main Methods:
- Utilized microbiota manipulation techniques and genetic mouse models.
- Employed single-cell RNA-sequencing for comprehensive myeloid cell profiling.
- Assessed CAMs in germ-free and conventionally-raised mice under homeostatic, viral infection, and Alzheimer's disease models (5xFAD mice).
Main Results:
- Complex microbiota tightly regulate choroid plexus macrophage numbers and transcriptional profiles under steady-state conditions.
- Perivascular and meningeal macrophages showed less sensitivity to microbiota compared to choroid plexus macrophages.
- Germ-free mice exhibited attenuated CAM immune responses during viral infection.
- Perivascular macrophages in germ-free 5xFAD mice demonstrated enhanced amyloid-beta uptake.
Conclusions:
- Gut microbiota play a distinct role in regulating CNS-associated macrophage populations and functions.
- Microbiota-macrophage interactions are crucial during CNS homeostasis and disease states like Alzheimer's.
- Understanding these interactions may offer therapeutic targets for neurological disorders.
