Model of the Sporozoite’s Journey in the Mammalian Host.

Migratory sporozoites (red) are injected into the dermis by an infected mosquito, where they encounter cells expressing undersulfated HSPGs (gray hexagons) and migrate through these cells to enter the blood circulation. In the liver they cross the sinusoidal barrier and encounter the highly sulfated HSPGs found in the loose basement membrane of the liver (space of Disse) and on hepatocytes (blue hexagons) and become activated for productive invasion (green sporozoites). The inset shows some of the specific steps involved in sporozoite activation, namely crosslinking of CSP by highly sulfated HSPGs, which results in CDPK6-dependent signaling that leads to the secretion of a cysteine protease (stars) that proteolytically processes surface CSP. Reproduced with modifications and permission from [25].