Comparative Review of Microglia and Monocytes in CNS Phagocytosis

Abstract

Macrophages maintain tissue homeostasis by phagocytosing and removing unwanted materials such as dead cells and cell debris. Microglia, the resident macrophages of the central nervous system (CNS), are no exception. In addition, a series of recent studies have shown that microglia phagocytose the neuronal synapses that form the basis of neural circuit function. This discovery has spurred many neuroscientists to study microglia. Importantly, in the CNS parenchyma, not only microglia but also blood-derived monocytes, which essentially differentiate into macrophages after infiltration, exert phagocytic ability, making the study of phagocytosis in the CNS even more interesting and complex. In particular, in the diseased brain, the phagocytosis of tissue-damaging substances, such as myelin debris in multiple sclerosis (MS), has been shown to be carried out by both microglia and blood-derived monocytes. However, it remains largely unclear why blood-derived monocytes need to invade the parenchyma, where microglia are already abundant, to assist in phagocytosis. We will also discuss whether this phagocytosis can affect the fate of the phagocytosing cell itself as well as the substance being phagocytosed and the surrounding environment in addition to future research directions. In this review, we will introduce recent studies to answer a question that often arises when studying microglial phagocytosis: under what circumstances and to what extent blood-derived monocytes infiltrate the CNS and contribute to phagocytosis. In addition, the readers will learn how recent studies have experimentally distinguished between microglia and infiltrating monocytes. Finally, we aim to contribute to the progress of phagocytosis research by discussing the effects of phagocytosis on phagocytic cells.

Immunoproteasomes control activation of innate immune signaling and microglial function

“…We observed increased expression of IBA-1 in ONX-0914 treated C20 cells comparison to control DMSO treated cells (Figures 7F, G). b5i/LMP7-deficient primary microglia exhibit increased phagocytic activity despite less activation in response to amyloid-beta Microglia are the resident macrophages of the brain and, as such are responsible for the clearance of apoptotic cells and potentially toxic protein aggregates (1)(2)(3). It is suggested that apoptotic cells and protein aggregates activate microglia to be phagocytosed by them (46).…”

“…Thanks to their capacity of sensing changes in their environment such as pathogens and/or small protein flux perturbations, microglia largely contribute to the surveillance of the central nervous system (CNS) (1)(2)(3). As microglia are in fact macrophages of the brain, they are able to phagocytose protein aggregates and pathogens to clear the environment and protect the brain from possible danger (2)(3)(4). Therefore, microglial function heavily relies on protein homeostasis and mediation of innate immune signaling.…”

Cross-Talk and Subset Control of Microglia and Associated Myeloid Cells in Neurological Disorders

“…Microglia primarily accomplish this via phagocytosis, a process through which cells recognize, engulf, and digest degraded cellular particles and debris. Following acquired brain injury, microglia are capable of acting as antigen-presenting cells to initiate activation of neighboring T-cells and orchestrate an inflammatory response that can impair proper neurological function [ 14 , 15 , 16 , 17 , 18 , 19 ]. In addition, microglia are activated following brain injury and undergo significant morphological changes to execute different tasks.…”

The effect of morphine on rat microglial phagocytic activity: an in vitro study of brain region-, plating density-, sex-, morphine concentration-, and receptor-dependency

“…In peripheral immune cells, morphine is repeatedly shown to decreases immune activation and phagocytosis in vivo and in vitro (Rojavin, Szabo et al 1993, Ninković and Roy 2012, Ninkovic, Anand et al 2016) dependent on dose (Borman, Ciepielewski et al 2009) and duration of exposure (Pagán, Figueroa et al 2001). Phagocytosis is an important immune effector that serves to clear damage, debris, and infection (Andoh and Koyama 2021). Unlike peripheral immune cells, the effect of morphine on microglia is less well studied.…”