2025/03/19 by Samuel G Chamberlain, Shiroh Iwanaga, Matthew K. Higgins · 1 voice
Immunology and Microbiology · Medicine · #Aquaculture disease management and microbiota #Malaria Research and Control #Mosquito-borne diseases and control
paper · doi:10.1016/j.mib.2025.102598
openalex publication_date 2025/03/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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. • Two protein families decorate erythrocytes infected by malaria parasites. • PfEMP1 tether infected erythrocytes to endothelial surfaces. • RIFINs bind to human immune receptors to suppress natural killer cell function. • Unusual broadly-inhibitory antibodies bind conserved regions as humans fight back.