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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia
Stephanie A Amici1, Joycelyn Dong1,2, Mireia Guerau-de-Arellano1,3,4,5
1School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United States.
Abstract:
Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.
Insights
Macrophages and microglia are key immune cells in the central nervous system. This review explores molecular pathways that shape their diverse phenotypes, crucial for understanding neuroinflammation in diseases like multiple sclerosis (MS).
Area of Science:
- Neuroimmunology and Cellular Biology
- Central Nervous System (CNS) Inflammation
Background:
- Macrophages and microglia are vital immune cells in the CNS, involved in development, homeostasis, and injury response.
- Diverse macrophage and microglial phenotypes exist, extending beyond the traditional M1/M2 inflammatory/resolution model.
- Understanding these phenotypes is critical for neuroinflammatory diseases like multiple sclerosis (MS).
Purpose of the Study:
- To comprehensively review molecular pathways modulating tissue macrophage and microglial phenotypes.
- To explore how environmental signals integrate into molecular programs controlling inflammatory responses.
- To identify therapeutic targets for modulating cellular programs to control excessive neuroinflammation.
Main Methods:
- Comprehensive literature review focusing on molecular pathways influencing macrophage and microglial phenotypes.
- Analysis of classic pathways, microRNAs, receptor-tyrosine kinases, and metabolism in phenotype modulation.
- Discussion of pathway parallels between microglia and peripheral macrophages, including novel identification markers.
Main Results:
- Macrophage and microglial phenotypes are complex, plastic, and influenced by diverse molecular pathways.
- Emerging roles of microRNAs, receptor-tyrosine kinases, and cellular metabolism significantly impact macrophage phenotypes.
- Novel markers can differentiate peripheral macrophages from microglia and indicate specific phenotypes.
Conclusions:
- Modulating molecular pathways offers opportunities to control excessive inflammation in neuroinflammatory diseases.
- A deeper understanding of macrophage and microglial plasticity is essential for therapeutic strategies in CNS disorders.
- Further research into phenotype-specific markers and pathways will advance treatment for conditions like MS.
