Getting in the blood

A team led by Alan Cowman of the Walter and Eliza Hall Institute of Medical Research in Australia has made a significant breakthrough in understanding how malaria parasites invade human red blood cells (erythrocytes)¹.

Malaria is a major killer in the tropics. Humans can become infected when bitten by mosquitoes carrying the malaria parasite. But to survive within the human host, the parasite must successfully invade erythrocytes.

Cowman’s team studied erythrocyte invasion by Plasmodium falciparum, which is responsible for the most severe form of human malaria.

Invasion involves the binding of molecular ‘ligands’ expressed by the parasite to receptor proteins on the erythrocyte surface. Some of these receptors contain sialic acid, whereas others do not. By expressing different ligands, P. falciparum can switch between sialic acid-dependent and -independent invasion pathways, helping it to evade the host’s immune system.

Cowman and his collaborators showed that a known protein called Complement receptor 1 (CR1) is the erythrocyte receptor for PfRh4, a major P. falciparum ligand essential for sialic acid-independent invasion. This is especially important because only ligand-receptor pairs involved in sialic acid-dependent invasion had been identified previously.

The researchers hope that their discovery will lead to the development of a vaccine capable of blocking erythrocyte invasion by malaria parasites.