Journal
ACTA NEUROPATHOLOGICA
Volume 143, Issue 2, Pages 179-224Publisher
SPRINGER
DOI: 10.1007/s00401-021-02384-2
Keywords
Microglia; Monocyte-derived cells; Immune-mediated pathology; Neuroinflammation; Neurodegeneration; Encephalitis
Categories
Funding
- National Health and Medical Research Council [1088242]
- Merridew Foundation
- Australian Government Research Training Stipend Scholarship
- University of Sydney Postgraduate Merit Award
- Merridew Foundation PhD Scholarship
- National Health and Medical Research Council of Australia [1088242] Funding Source: NHMRC
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Microglia and monocytes play crucial roles in neurological diseases, but the lack of discriminating markers and experimental systems has historically hindered the precise definition of their roles. Recent advancements in single-cell technologies, new markers, and drugs have improved the ability to distinguish these cell types, yet limitations in focusing on specific cell types, diseases or experimental approaches have restricted the broader connections between phenotype and function.
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.
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