Plasmodium sporozoite-host interactions from the dermis to the hepatocyte

Abstract

Sporozoites are the infective stage of the malaria parasite. They are deposited in the skin by infected Anopheles mosquitoes and must penetrate cell barriers in the skin and liver sinusoid to reach their target cell, the hepatocyte, where they enter in a vacuole and begin development into the next life cycle stage, the exoerythrocytic form. Recent advances in our understanding of sporozoite biology in the dermal inoculation site, the role of cell traversal and the mechanism by which sporozoites productively invade hepatocytes will be highlighted in this review.

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].