Abstract
In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population. These cells function to maintain homeostasis and are directly involved in the development and resolution of neuroinflammatory processes. Also, following inflammation, circulating monocytes can be recruited and enter the CNS, therefore contributing to brain pathology. These cell populations have now been identified as key players in CNS pathology, including autoimmune diseases, such as multiple sclerosis, and degenerative diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease. Here, we review the evidence on the involvement of CNS macrophages in neuroinflammation and the advantages, pitfalls, and translational opportunities of pharmacological interventions targeting these heterogeneous cellular populations for the treatment of brain diseases.
Highlights
The central nervous system (CNS), as an “immuno-privileged” organ, hosts numerous populations of myeloid cells and defensive barriers such as the meninges, the perivascular space, and the choroid plexus [1]
Receptor for Advanced Glycation End-products (RAGE) is highly expressed in the CNS cells including microglia, neurons, and endothelial cells and contributes to many pathological states characterized by an inflammatory component [54]
Khoury et al have shown that the deletion of chemokine receptor 2 (CCR2) in an Alzheimer’s disease (AD) mouse model resulted in a substantial reduction of microglial accumulation around the plaque and an increase in the deposition of Aβ [93], demonstrating that the chemokine CCR2 mediates the recruitment of inflammatory peripherals monocytes in the Alzheimer’s brain [94]
Summary
The central nervous system (CNS), as an “immuno-privileged” organ, hosts numerous populations of myeloid cells and defensive barriers such as the meninges, the perivascular space, and the choroid plexus [1]. Under steady-state conditions, the central myeloid cell populations in the CNS are represented by parenchymal microglia and non-parenchymal macrophages, namely perivascular macrophages, meningeal macrophages, macrophages of the choroid plexus, and blood-borne monocytes [2,3] (Figure 1). All of these populations are characterized by specific localization and molecular profiles [2,3]. Microglia are a unique tissue-resident macrophage population of the CNS and are considered to be primarily involved in immune reactions and inflammatory diseases [4]. Sci. 2018, 19, x FOR PEER REVIEW population of the CNS and are considered to be primarily involved in immune reactions and inflammatory diseases [4]
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