The Meninges as CNS Interfaces and the Roles of Meningeal Macrophages

The brain, the most important component of the central nervous system (CNS), is protected by multiple intricate barriers that strictly regulate the entry of proteins and cells. Thus, the brain is often described as an organ with immune privilege. Within the brain parenchyma, microglia are thought to be the primary resident immune cells, with no other immune-related cells present under normal conditions. On the other hand, recent studies in the meningeal border regions have revealed the presence of meningeal-specific lymphatic vessels and channels that connect to the skull bone marrow. Importantly, resident macrophage populations specific to these boundary regions, known as CNS-associated macrophages (CAMs) or border-associated macrophages (BAMs), have been identified. In contrast to the brain parenchyma, the meninges contain many immune-related structures and cells, making them an important immune interface at the CNS border. CAMs serve a dual function, triggering immune responses under pathological conditions and supporting the maintenance of brain homeostasis. This review focuses on the immune architecture of the meninges and the roles of CAMs in humans and mice, summarizing and discussing recent advances in this field.