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Updated: Oct 11, 2025

Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function
Alanna G Spiteri1,2,3,4, Claire L Wishart1,2,3,4, Roger Pamphlett5,6
1Viral Immunopathology Laboratory, Infection, Immunity and Inflammation Research Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.
Abstract:
In neurological diseases, the actions of microglia, the resident myeloid cells of the CNS parenchyma, may diverge from, or intersect with, those of recruited monocytes to drive immune-mediated pathology. However, defining the precise roles of each cell type has historically been impeded by the lack of discriminating markers and experimental systems capable of accurately identifying them. Our ability to distinguish microglia from monocytes in neuroinflammation has advanced with single-cell technologies, new markers and drugs that identify and deplete them, respectively. Nevertheless, the focus of individual studies on particular cell types, diseases or experimental approaches has limited our ability to connect phenotype and function more widely and across diverse CNS pathologies. Here, we critically review, tabulate and integrate the disease-specific functions and immune profiles of microglia and monocytes to provide a comprehensive atlas of myeloid responses in viral encephalitis, demyelination, neurodegeneration and ischemic injury. In emphasizing the differential roles of microglia and monocytes in the severe neuroinflammatory disease of viral encephalitis, we connect inflammatory pathways common to equally incapacitating diseases with less severe inflammation. We examine these findings in the context of human studies and highlight the benefits and inherent limitations of animal models that may impede or facilitate clinical translation. This enables us to highlight common and contrasting, non-redundant and often opposing roles of microglia and monocytes in disease that could be targeted therapeutically.
Insights
Microglia and monocytes have distinct roles in neurological diseases. Understanding their specific functions in conditions like viral encephalitis and neurodegeneration is key for developing targeted therapies.
Area of Science:
- Neuroimmunology
- Cellular and Molecular Neuroscience
Background:
- Microglia and infiltrating monocytes are key myeloid cells in the central nervous system (CNS).
- Their distinct roles in driving immune-mediated pathology in neurological diseases are often conflated due to a lack of specific markers and experimental systems.
- Recent advancements in single-cell technologies and specific markers have improved our ability to differentiate these cell types in neuroinflammation.
Purpose of the Study:
- To critically review, tabulate, and integrate disease-specific functions and immune profiles of microglia and monocytes.
- To provide a comprehensive atlas of myeloid cell responses across diverse CNS pathologies, including viral encephalitis, demyelination, neurodegeneration, and ischemic injury.
- To highlight the differential, non-redundant, and often opposing roles of microglia and monocytes in disease for potential therapeutic targeting.
Main Methods:
- Comprehensive literature review and data integration.
- Critical analysis of disease-specific functions and immune profiles of microglia and monocytes.
- Comparison of findings across viral encephalitis, demyelination, neurodegeneration, and ischemic injury models.
Main Results:
- Detailed atlas of microglia and monocyte functions and immune profiles in various neurological diseases.
- Emphasis on differential roles in viral encephalitis, linking inflammatory pathways to other CNS pathologies.
- Identification of common, contrasting, and opposing roles of microglia and monocytes in disease pathogenesis.
Conclusions:
- Microglia and monocytes exhibit distinct and often opposing roles in neurological disease.
- A comprehensive understanding of these myeloid cell dynamics is crucial for developing targeted neuroimmunological therapies.
- Translational challenges and benefits of animal models in studying these cell types are highlighted.
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