Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function

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.