The Survival Strategies of Malaria Parasite in the Red Blood Cell and Host Cell Polymorphisms

Figure 1

(i) Erythrocytes infected with mature forms of P. falciparum parasites (pigmented trophozoites and schizonts) have the ability to bind to vascular endothelium of various organs and tissues such as heart, lung, brain, muscle, and adipose tissue (sequestration), uninfected erythrocytes (rosetting), and platelets (platelet-mediated clumping) thus, allowing only young ring forms of the parasite to be detected in human peripheral blood samples. Rosetting and platelet-mediated clumping are phenotypes that are displayed by some but not all P. falciparum isolates, and the PfEMP1 variants that mediate rosetting are predominantly of the group A type, which do not adhere to CD36. Owing to the fact that heparan sulphate mediates binding of rosetting IEs to endothelial cells, it is unclear whether binding of IE to heparan sulphate on endothelial cells occurs independently of rosetting, or all parasites that bind heparan sulphate form rosettes. Although three receptors for cytoadherence have been identified for platelet clumping, the molecular mechanisms of the interaction of P. falciparum ligands with platelets are not fully understood, and PfEMP1 is thought to be a likely candidate molecule. Furthermore, these receptors do not form clump in all the cases and suggest the participation of distinct epitopes on these receptors or additional platelet receptors in clumping formation. (ii) The predicted domain organization and binding properties of PfEMP-1to different host receptors. Arrow from the receptors to PfEMP1 domain indicates their respective binding sites, and for other receptors, the binding domains are yet to be identified. A: Erythrocyte, B: Infected erythrocyte, C: Infected erythrocyte at pigmented trophozoite stage, D: Platelet, and E: Leukocyte.