Microglial Corpse Clearance: Lessons From Macrophages.

Mar Márquez-Ropero,Ainhoa Plaza-Zabala,Amanda Sierra,Eva Benito

doi:10.3389/fimmu.2020.00506

Abstract

From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we will first summarize the differences in the origin, lineage and population maintenance of microglia and macrophages. Then, we will discuss several principles that govern macrophage phagocytosis of apoptotic cells (efferocytosis), including the existence of redundant recognition mechanisms (“find-me” and “eat-me”) that lead to a tight coupling between apoptosis and phagocytosis. We will then describe that resulting from engulfment and degradation of apoptotic cargo, phagocytes undergo an epigenetic, transcriptional and metabolic rewiring that leads to trained immunity, and discuss its relevance for microglia and brain function. In summary, we will show that neuroimmunologists can learn many lessons from the well-developed field of macrophage phagocytosis biology.

Highlights

Frontiers in ImmunologyFrom development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates
Microglial phagocytosis of apoptotic cells is at the core of the brain regenerative response
Its relevance in maintaining brain tissue homeostasis from development to aging and neurodegenerative diseases is undisputed but, many fundamental questions about the biology of the process remain open: How is phagocytosis efficiency regulated at the cellular and molecular levels? How can it be manipulated? Is it a dead-end road or does it trigger changes in the phagocyte? Is phagocytosis a process of garbage removal or does it actively participate in the well-being of the surrounding tissue? We here try to address these questions by collecting answers from microglia’s cousins, the macrophages that reside in other tissues

Summary

Frontiers in Immunology

From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. The brain is equipped with efficient phagocytes: the microglia. We will discuss several principles that govern macrophage phagocytosis of apoptotic cells (efferocytosis), including the existence of redundant recognition mechanisms (“find-me” and “eat-me”) that lead to a tight coupling between apoptosis and phagocytosis. We will describe that resulting from engulfment and degradation of apoptotic cargo, phagocytes undergo an epigenetic, transcriptional and metabolic rewiring that leads to trained immunity, and discuss its relevance for microglia and brain function. We will show that neuroimmunologists can learn many lessons from the well-developed field of macrophage phagocytosis biology

INTRODUCTION

LINEAGE AND ORIGINS OF MICROGLIA AND OTHER MACROPHAGES

PHAGOCYTOSIS BY MACROPHAGES AND MICROGLIA

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