Microglial heterogeneity: distinct cell types or differential functional adaptation?

Savannah D Benusa,Jeffrey L Dupree,Nicholas M George

doi:10.20517/2347-8659.2020.03

Abstract

Microglial heterogeneity: distinct cell types or differential functional adaptation?

Highlights

Microglia, the resident immune cells of the central nervous system (CNS), were first characterized 100 years ago by Pio del Rio Hortega but our understanding of their function remains incomplete
Disease-Associated Microglia (DAM) can downregulate homeostatic genes including P2ry12, Cx3Cr1, and transmembrane protein 119 (Tmem119), and upregulate genes in either a triggering receptor expressed on myeloid cells 2 (Trem2) dependent (Axl, C-type lectin domain containing 7A, secreted phosphoprotein 1) or independent (Apolipoprotein E, TYRO protein tyrosine kinase-binding protein) manner[91]
We are beginning to appreciate their critical roles in disease, potentially both as CNS protectors by recognizing and removing infected, dying and dead cells, and as CNS villains secondary to hyperactivation or dysregulation

Summary

INTRODUCTION

The resident immune cells of the central nervous system (CNS), were first characterized 100 years ago by Pio del Rio Hortega (reviewed in[1]) but our understanding of their function remains incomplete. Microglia from all three models presented proinflammatory profiles, the microglia from each expressed a unique set of factors suggesting environmentalspecific responses These observations are consistent with environmental cues driving heterogeneity, it remains possible, and perhaps likely, that microglia represent intrinsically distinct populations. DAM can downregulate homeostatic genes including P2ry, Cx3Cr1, and transmembrane protein 119 (Tmem119), and upregulate genes in either a triggering receptor expressed on myeloid cells 2 (Trem2) dependent (Axl, C-type lectin domain containing 7A, secreted phosphoprotein 1) or independent (Apolipoprotein E, TYRO protein tyrosine kinase-binding protein) manner[91] Another related class of microglia, which present with a similar expression profile as DAM[94], was recently described and named microglial degenerative phenotype (MGnD). Perhaps most interesting is the finding that specific subpopulations of microglia were represented in demyelinating lesions in the mouse and human brains, suggesting that microglial cluster expression profiles may allow identifying disease-specific“fingerprints”, and eventually aid in human disease treatment

CONCLUSION

Findings

Availability of data and materials