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Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic
E Ulvestad1, K Williams, R Bjerkvig
1Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway.
Abstract:
Resting microglia comprise up to 13% of the cells in human central nervous system (CNS) white matter. Their large number and dendritic morphology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and transform into typical phagocytic macrophages. Microglia have been implicated as the main antigen presenting cell within the CNS, and appear to be of central importance as effectors and regulators of demyelination. To further characterize the capacity for immune reactivity within the human CNS, we have studied several characteristics of microglia, both in situ and in vitro. We find that human microglia have ultrastructural, phenotypic (CD11c, CD68, acid phosphatase), and functional (FcR and CR mediated phagocytosis) properties typical for cells of the monocyte lineage. Our data indicate that microglia also have properties in common with dendritic antigen-presenting cells. Electron microscopy studies show extended dendritic cell processes on cultured microglia, and microglia are, like dendritic cells, negative for the monocyte markers nonspecific esterase, endogenous peroxidase, CD14, and RFD7. Microglia constitutively express HLA-DR in situ, and express the dendritic cell marker RFD1 upon activation. Coculturing of microglia with CD4+ T cells results in clustering of T cells around microglia and initiation of a mixed lymphocyte reaction, both distinguishing features of dendritic cells. These functional properties of microglia may be of importance for the maintenance of an immunologic response in the CNS, an organ where dendritic cells, in contrast to other organs, have not previously been identified.
Insights
Human microglia, abundant in the central nervous system (CNS), function like dendritic cells in immune responses. These cells present antigens and regulate demyelination, crucial for CNS immunity.
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Microglia are the primary immune cells in the human central nervous system (CNS), constituting up to 13% of white matter cells.
- Their morphology and abundance suggest a key role in surveying the CNS for threats and regulating immune responses, including demyelination.
Purpose of the Study:
- To investigate the immune reactivity and antigen-presenting capabilities of human microglia.
- To compare microglial characteristics with those of monocyte lineage cells and dendritic cells.
Main Methods:
- In situ and in vitro studies of microglial ultrastructure and phenotype (CD11c, CD68, acid phosphatase, HLA-DR, RFD1).
- Functional assays including Fc receptor (FcR) and complement receptor (CR) mediated phagocytosis.
- Coculturing microglia with CD4+ T cells to assess mixed lymphocyte reactions.
Main Results:
- Human microglia exhibit ultrastructural, phenotypic, and functional characteristics of both monocyte lineage cells and dendritic antigen-presenting cells.
- Cultured microglia display dendritic cell-like processes and are negative for monocyte markers (CD14, RFD7).
- Microglia express HLA-DR and RFD1 upon activation, and stimulate T cells in a mixed lymphocyte reaction.
Conclusions:
- Human microglia possess properties of dendritic cells, suggesting a significant role in initiating and maintaining immune responses within the CNS.
- These findings highlight microglia's importance in CNS immunity, particularly in an organ where dendritic cells were not previously identified.