Figure 1. Mechanisms by which C. neoformans has been posited to enter the central nervous system.

C. neoformans can travel in blood in either free or phagocytic cell–associated form. Free yeast forms in blood could originate from exocytosis from phagocytic cells or perhaps transmigration from primary infection areas such as the lung. (i) The Trojan horse mechanism. C. neoformans reaches the brain inside an infected phagocytic cell that transports it across from the lumen of a brain capillary to the central nervous system. (ii) Direct transcytosis. C. neoformans reaches the brain by direct transmigration of capillary endothelium.