Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes

Remnants of lipoproteins (chylomicron remnants and very low density lipoprotein remnants) are rapidly cleared from plasma and enter hepatocytes. The catabolism of the lipoproteins is apolipoprotein E (apoE) dependent. It has been suggested that the lipoproteins are initially captured in the space of Disse by heparan sulfate proteoglycans and then internalized by members of the LDL-receptor gene family. Within minutes after injection by Anopheles mosquitoes, malaria sporozoties are also removed from the blood circulation by the liver. The sporozoite's surface is covered by the circumsporozoite protein (CS), and its region ll-plus has been implicated in the initial binding of the parasites to the hepatocytes. Here we provide evidence that CS and remnant lipoproteins compete in vitro and in vivo for the same liver receptors. As predicted by these observations, apoE-enriched remnant lipoproteins inhibit sporozoite invasion of HepG2 cells, and malaria parasites are less infective in LDL-receptor knockout mice maintained on a high fat diet.