Malaria is a global health problem and causes 2 – 3 million deaths each year. Mosquito bites allow malaria parasites to enter the bloodstream. Within 30 minutes, the parasites are transported to the liver where they enter cells and start to reproduce rapidly. Following release from hepatocytes, the parasites re-enter the bloodstream and infect red blood cells, triggering the pathology that is associated with malaria.
The receptor on human liver cells that allows the malaria parasites to enter hepatocytes has been identified as the scavenger receptor (SR-B1). This receptor normally transfers cholesteryl esters and other lipids from high density lipoprotein (HDL) in the bloodstream into liver cells. A new study shows that, in cell culture experiments as well as experiments in mice, blocking the SR-B1 receptor dramatically reduced the ability of the malaria parasite to infect liver cells. The researchers used RNA interference (RNAi), monoclonal antibodies, and small molecule inhibitors to demonstrate the importance of the SR-B1 receptor for entry of malaria parasites into hepatocytes. The study demonstrates that blocking the SR-B1 receptor may offer a new approach to the prophylaxis of malaria.
Targeting host mechanisms promises better protection against the emergence of resistant strains of the malaria parasite but, in this case, should be balanced against the atherosclerotic potential of long term blockade of the SR-B1 receptor.