Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function.
Alanna G SpiteriClaire L WishartRoger PamphlettGiuseppe LocatelliNicholas Jonathan Cole KingPublished in: Acta neuropathologica (2021)
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.
Keyphrases
- dendritic cells
- inflammatory response
- single cell
- neuropathic pain
- peripheral blood
- oxidative stress
- blood brain barrier
- endothelial cells
- lipopolysaccharide induced
- induced apoptosis
- bone marrow
- cerebral ischemia
- rna seq
- stem cells
- traumatic brain injury
- ischemia reperfusion injury
- early onset
- cell proliferation
- brain injury
- patient safety
- cell death
- case control
- induced pluripotent stem cells
- endoplasmic reticulum stress