Intravital Observation of Plasmodium berghei Sporozoite Infection of the Liver
The dual blood supply of the liver, consisting of branches of the portal vein and the hepatic artery, merges upon entry into the liver lobule at the portal field. The blood flows along the sinusoid and exits at the central vein. First sporozoites enter the liver lobule either via the portal vein or the hepatic artery, and then are abruptly arrested by binding to the sinusoidal cell layer. The initial binding is presumably mediated by stellate-cell-derived ECM proteoglycans that protrude from the space of Disse across the endothelial sieve plates into the sinusoidal lumen. After a pause, the parasites begin to glide along the sinusoid, frequently moving against the bloodstream, until they then encounter a Kupffer cell, on the surface of which they recognize selected chondroitin and heparan sulfate proteoglycans. Sporozoites position themselves with their apical cell pole facing the phagocyte. After a considerable pause, they slowly pass through the Kupffer cell and cross the space of Disse beyond it, exhibiting a clearly visible constriction. Once inside the liver parenchyma, the parasites increase their velocity and migrate for many minutes through several hepatocytes, before they eventually settle down in a final one for EEF development. Sporozoite transmigration results in a trail of necrotic hepatocytes, whose remains are subsequently removed by infiltrating inflammatory cells.