Immune evasion runs in the family: two surface protein families of Plasmodium falciparum–infected erythrocytes

Abstract

Two protein families are found on the surfaces of erythrocytes infected with Plasmodium falciparum, a causative agent of deadly malaria. PfEMP1 are tethers binding endothelial receptors and holding infected erythrocytes to tissue and blood vessel surfaces, away from splenic clearance. RIFINs interact with immune receptors on natural killer cells, suppressing infected erythrocyte destruction. Both have expanded into families of diverse members to allow antigenic variation but retain surfaces of conserved chemistry and shape to bind human receptors. Recently discovered broadly inhibitory antibodies target one such surface on many EPCR-binding PfEMP1. Remarkable antibodies take this one step further, directly incorporating ectodomains of immune receptors into their loops, allowing RIFIN recognition. Finally, some RIFINs are targets of activating killer immune receptors, helping natural killer cells destroy infected erythrocytes. Studies of these two families therefore reveal a snapshot of the battle between this ancient parasite and the immune system of its human host.