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Separate precursor cells for macrophages and microglia in mouse brain: immunophenotypic and immunoregulatory
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. bill.walker@st.jude.org
Abstract:
The brain contains two populations of macrophages: the microglia of brain parenchyma, and the central nervous system (CNS) macrophages located in the perivascular spaces, the leptomeninges and the choroid plexus. The microglia are characterized, in part, by their paucity of major histocompatibility complex (MHC) molecules and lack of constitutive antigen (Ag)-presenting activity for naïve CD4+ T-cells. Some CNS macrophages, on the other hand, constitutively express MHC molecules and present Ag to naïve CD4+ T-cells. We have reported that mouse brain contains precursor cells that, in the presence of colony-stimulating factor-1, the macrophage growth factor, give rise to clones of cells that differ in their ability to constitutively present Ag to naive CD4+ T cells. Here we report that this population of precursor cells can be separated into two discrete subpopulations based on differences in cell density and that the two cell populations give rise to progeny that differ in their content of cells constitutively expressing MHC class II and CD86 molecules, and the ability to present Ag to naïve CD4+ T-cells. A comparison of the level of CD45 staining of the progeny, an indication of a microglial or a CNS macrophage origin, suggests that one population of precursor cells yields immunologically immature microglia and the other CNS macrophages.
Insights
Brain macrophages, microglia and CNS macrophages, originate from distinct precursor cells. Density separation of these precursors reveals distinct progeny with differing immune-presenting capabilities, clarifying their developmental pathways.
Area of Science:
- Neuroimmunology
- Cell Biology
- Immunology
Background:
- The brain harbors two distinct macrophage populations: microglia within the parenchyma and CNS macrophages in associated structures.
- Microglia typically exhibit low major histocompatibility complex (MHC) expression and limited antigen-presenting capacity for naive CD4+ T-cells.
- CNS macrophages constitutively express MHC molecules and possess antigen-presenting activity for naive CD4+ T-cells.
Purpose of the Study:
- To investigate the heterogeneity of brain macrophage precursor cells.
- To determine if distinct precursor subpopulations give rise to microglia and CNS macrophages with differential immunological properties.
- To elucidate the developmental origins of brain macrophage populations.
Main Methods:
- Isolation and density-based separation of mouse brain precursor cells.
- Culture of precursor cells with colony-stimulating factor-1 (CSF-1).
- Analysis of progeny cell populations for MHC class II and CD86 expression, and antigen-presenting capacity for naive CD4+ T-cells.
- Assessment of CD45 staining to differentiate microglial and CNS macrophage origins.
Main Results:
- Mouse brain precursor cells can be separated into two distinct subpopulations based on cell density.
- These subpopulations yield progeny with differing levels of MHC class II and CD86 expression.
- The progeny also exhibit distinct capacities for antigen presentation to naive CD4+ T-cells, with one population yielding immature microglia and the other CNS macrophages.
Conclusions:
- Distinct precursor cell populations exist within the brain, giving rise to microglia and CNS macrophages.
- Differential expression of immune molecules and antigen-presenting function correlate with precursor cell density and progeny type.
- This study clarifies the developmental dichotomy of brain macrophages, impacting our understanding of neuroinflammation and immune surveillance in the CNS.