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.
Highlights
The central nervous system (CNS), consisting of the brain and the spinal cord, is separated from the periphery by the presence of the blood–brain barrier (BBB), meninges, and the choroid plexus [1,2,3].Since the major immune cells present in the parenchyma are microglia [4,5], unwanted materials in the parenchyma are removed mainly by microglial phagocytosis under physiological conditions [6,7]
Fiala et al compared the amount of Aβ phagocytosis by monocytes and macrophages from the blood of healthy subjects and patients with Alzheimer’s disease (AD) and found that cells from AD patients had a lower phagocytic capacity [91]. These results indicate that macrophages are able to phagocytose Aβ and that impaired phagocytosis of Aβ by macrophages may contribute to the development of AD
It should be noted that the degree of BBB disruption and the type and amount of proinflammatory cytokines secreted by each model may differ, resulting in different degrees of monocyte infiltration, which may determine whether monocytes can phagocytose synapses
Summary
The CNS, consisting of the brain and the spinal cord, is separated from the periphery by the presence of the blood–brain barrier (BBB), meninges, and the choroid plexus [1,2,3]. In diseases with physical damage or excessive inflammatory responses, blood-derived monocytes infiltrate the parenchyma due to a loosening or disruption of the BBB [7,13,14]. These monocytes infiltrating the parenchyma have been shown to exert phagocytic activity in various diseases [7,13]. Because microglia and blood-derived monocytes have different cell lineages and gene expression [6,19,20], differences in phagocytic capacity are expected.
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