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The phenotypic convergence between microglia and peripheral macrophages during development and neuroinflammation
Francesca Grassivaro1, Gianvito Martino2, Cinthia Farina1
1Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Abstract:
Microglia, the tissue resident macrophages of the brain, are increasingly recognized as key players for central nervous system development and homeostasis. They are long-lived cells deriving from a transient wave of yolk-sac derived erythro-myeloid progenitors early in development. Their unique ontology has prompted the search for specific markers to be used for their selective investigation and manipulation. The first generation of genome-wide expression studies has provided a bundle of transcripts (such as Olfml3, Fcrls, Tmem119, P2ry12, Gpr34, and Siglech) useful to distinguish microglia from peripheral macrophages. However, more recent reports have revealed that microglial phenotype is constantly shaped by the microenvironment in a time-, and context-dependent manner. In this article, we review data that provide additional pieces to this complex scenario and show the existence of unexpected phenotypic convergence between microglia and peripheral macrophages at certain developmental stages and under pathological conditions. These observations suggest that the two cell types act synergically boosting their mutual activities depending on the microenvironment. This novel information about the biology of microglia and peripheral macrophages sheds new light about their therapeutic potential for neuroinflammatory and neurodegenerative diseases.
Insights
Microglia, brain macrophages, share surprising similarities with peripheral macrophages in certain conditions. This convergence highlights their synergistic roles and therapeutic potential for brain diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are brain-resident macrophages crucial for central nervous system (CNS) development and homeostasis.
- Their unique origin from yolk-sac progenitors necessitates specific markers for differentiation from peripheral macrophages (e.g., Tmem119, P2ry12).
- Microglial phenotype is dynamic, influenced by the microenvironment in a time- and context-dependent manner.
Purpose of the Study:
- To review current data on microglial and peripheral macrophage biology.
- To highlight phenotypic convergence between these cell types under specific conditions.
- To explore the implications for neuroinflammation and neurodegenerative diseases.
Main Methods:
- Review of existing scientific literature and data.
- Analysis of transcriptomic and phenotypic studies.
- Synthesis of information on microglial and peripheral macrophage interactions.
Main Results:
- Genome-wide studies identified initial markers distinguishing microglia from peripheral macrophages.
- Recent findings reveal unexpected phenotypic similarities between microglia and peripheral macrophages.
- These similarities emerge during specific developmental stages and in pathological contexts.
- Microglia and peripheral macrophages exhibit synergistic interactions influenced by the microenvironment.
Conclusions:
- The distinction between microglia and peripheral macrophages is not absolute and can blur under certain circumstances.
- Phenotypic convergence suggests a dynamic interplay and mutual functional enhancement.
- Understanding this interplay offers new therapeutic strategies for neuroinflammatory and neurodegenerative disorders.
