Microglia cells are the unique residential macrophages of the central nervous system (CNS). They have a special origin, as they derive from the embryonic yolk sac and enter the developing CNS at a very early stage. They play an important role during CNS development and adult homeostasis. They have a major contribution to adult neurogenesis and neuroinflammation. Thus, they participate in the pathogenesis of neurodegenerative diseases and contribute to aging. They play an important role in sustaining and breaking the blood-brain barrier. As innate immune cells, they contribute substantially to the immune response against infectious agents affecting the CNS. They play also a major role in the growth of tumours of the CNS. Microglia are consequently the key cell population linking the nervous and the immune system. This review covers all different aspects of microglia biology and pathology in a comprehensive way.
Microglia as the resident innate immune cells of the brain share common characteristics with monocyte-macrophage lineage such as expression of surface markers and chemokine/cytokine receptors. To date, there is no standardized simple model available to investigate the biology of human microglia. The aim of this study is to establish a new in vitro microglia model using blood-derived precursor cells. For that purpose, human peripheral blood monocytes were cultured in serum free medium in the presence of M-CSF, GM-CSF, NGF and CCL2 to generate monocyte-derived microglia (M-MG).M-MG were clearly different in morphology, phenotype and function from freshly isolated monocyte-derived dendritic cells (M-DC).M-MG acquired a ramified morphology with primary and secondary processes .M-MG displayed a comparable phenotype to the human microglia cell line HMC3, expressing very low levels of CD45, CD14 and HLA-DR, CD11b and CD11c; and a distinct pattern of chemokine receptors (CCR1, CCR2, CCR4, CCR5, CXCR1, CXCR3, CX3CR1).In comparison with M-DC, M-MG displayed lower T-lymphocyte stimulatory capacity as well as lower phagocytosis activity.The described protocol for the generation of human monocyte-derived microglia is feasible, well standardized and reliable, as it uses well defined culture medium and recombinant cytokines, but no serum or conditioned medium. This protocol will certainly be very helpful for future studies investigating the biology and pathology of human microglia.
Microglia are the macrophages of the central nerve system expressing various markers of the monocyte‐macrophage lineage such as surface molecules, chemokine/cytokine receptors, and displaying corresponding functions, including phagocytosis and antigen presentation. The aim of this study is to establish a new in vitro microglia model using blood‐derived precursor cells.For that purpose, human blood derived monocytes were cultured in the presence of a panel of cytokines and chemokines to generate in vitro microglia. The cells were further characterized for morphological, functional and phenotypic properties and compared with monocytes and in vitro generated dendritic cells. Monocytic lineage marker (CD45, CD14, HLA‐ DR) and chemokine receptors CCR1, CCR2, CCR4, CCR5, CXCR1 and CXCR3 were studied. In vitro generated microglia cells were different from monocytes and dendritic cells in morphology, function and expression of surface markers. In comparison with immature dendritic cells, microglia showed lower capacity in phagocytosing bacteria, antigen presentation and T lymphocyte stimulation.In conclusion, a new protocol for in vitro culture of human microglia cells has been established. Further studies to characterize the microglia at molecular level and use them for functional and toxicity studies are ongoing.Grant Funding Source: School funding
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