Functional diversity of microglia – how heterogeneous are they to begin with?
Open Access
- 1 January 2013
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cellular Neuroscience
- Vol. 7, 65
- https://doi.org/10.3389/fncel.2013.00065
Abstract
Microglia serve in the surveillance and maintenance, protection and restoration of the CNS homeostasis. By their parenchymal location they differ from other CNS-associated myeloid cells, and by origin as well as functional characteristics they are also‒at least in part‒distinct from extraneural tissue macrophages. Nevertheless, microglia themselves may not comprise a uniform cell type. CNS regions vary by cellular and chemical composition, including white matter (myelin) content, blood-brain barrier properties or prevaling neurotransmitters. Such a micromilieu could instruct as well as require local adaptions of microglial features. Yet even cells within circumscribed populations may reveal some specialization by subtypes, regarding house-keeping duties and functional capacities upon challenges. While diversity of reactive phenotypes has been established still little is known as to whether all activated cells would respond with the same program of induced genes and functions or whether responder subsets have individual contributions. Preferential synthesis of a key cytokine could asign a master control to certain cells among a pool of activated microglia. Critical functions could be sequestered to discrete microglial subtypes in order to avoid interference, such as clearance of endogeneous material and presentation of antigens. Indeed, several and especially a number of recent studies provide evidence for the constitutive and reactive heterogeneity of microglia by and within CNS regions. While such a principle of ‘division of labor’ would influence the basic notion of ‘the’ microglia, it could come with the practival value of addressing separate microglia types in experimental and therapeutic manipulations.Keywords
This publication has 105 references indexed in Scilit:
- Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activationHuman Immunology, 2009
- Trophic macrophages in development and diseaseNature Reviews Immunology, 2009
- Gene-specific control of the TLR-induced inflammatory responseClinical Immunology, 2009
- Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and Plasticity in Lineage Fate Determination of Differentiating CD4+ T CellsImmunity, 2009
- Exploring the full spectrum of macrophage activationNature Reviews Immunology, 2008
- IL-13 induces the expression of the alternative activation marker Ym1 in a subset of testicular macrophagesJournal of Reproductive Immunology, 2008
- How dying cells alert the immune system to dangerNature Reviews Immunology, 2008
- Macrophage activation by endogenous danger signalsThe Journal of Pathology, 2007
- A Rose by Any Other Name? The Potential Consequences of Microglial Heterogeneity During CNS Health and DiseaseNeurotherapeutics, 2007
- Monocyte and macrophage heterogeneityNature Reviews Immunology, 2005