Figure 1

Innate immunity profile in the healthy brain. Intact blood–brain barrier (BBB) formed by tightly sealed endothelial cells (EC) and the basal lamina containing extracellular matrix components (for example, collagen, fibronectin). The BBB restricts entry into the brain of pathogens, toxins and blood-borne molecules, such as immunoglobulin, albumin, thrombin, plasmin, fibrin and laminin. Bone marrow-derived circulating monocytes are divided in two main subsets, which are the patrolling anti-inflammatory (Ly6C^low) monocytes and the circulating proinflammatory (Ly6C^high) monocytes. Ly6C^low monocytes are long-lived cells that ensure continuous surveillance by crawling on blood vessel lumen. Ly6C^high monocytes are short-lived cells that are present in blood circulation. Perivascular macrophages (PM) probably arise from Ly6C^low monocytes and contribute to the maintenance of homeostasis of the perivascular space, mainly via its phagocytic activity. Quiescent microglia (QM) maintain a healthy brain microenvironment suitable for neurons (N), by continuously sensing any occurring changes via their high ramifications, secreting neurotrophic factors, namely brain-derived neurotrophic factor, and promoting neuronal remodeling and synaptic plasticity.