Rapid switching to multiple antigenic and adhesive phenotypes in malaria

Abstract

ADHESION of parasitized erythrocytes to post-capillary venular endothelium1or uninfected red cells'2–4 is strongly implicated in the pathogenesis of severe Plasmodlum faldparum malaria. Neo-antigens at the infected red-cell surface adhere to a variety of host receptors5–9, demonstrate serological diversity in field isolates10,11 and may also be a target of the host-protective immune response12. Here we use sequential cloning ofP. faldparum by micromanipula-tion to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, 'auto-agglutination' of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity.