Figure 1.

Overview of the main structures and cells of the central nervous system (CNS). The meninges is a complex membrane structure surrounding the brain and spinal cord, and is composed of a series of layers in which several immune cells are found. Cerebrospinal fluid (CSF) flows through the sub-arachnoid space here, and drains into the lymph nodes via lymphatic vessels (not shown). Astrocytes form barriers along the meninges and blood–brain barrier (BBB) and largely control cellular movement into the CNS. Microglia are found within the parenchyma, and exhibit a dendritic morphology when resting. Upon interaction with microbes, microglia activate and appear amoeboid in morphology. C. neoformans enters the parenchyma either as free yeast cells (following interaction with brain microvascular endothelial cells (BMECs)) or within infected macrophages (Trojan Horse phagocytes) from the brain microvasculature. Arrows represent movement of C. neoformans into the brain parenchyma, and resulting activation and cytokine production by microglia.