Insights into the Cytoadherence Phenomenon of Plasmodium vivax: The Putative Role of Phosphatidylserine

Abstract

Plasmodium vivax is the most geographically widespread and the dominant human malaria parasite in most countries outside of sub-Saharan Africa and, although it was classically recognized to cause benign infection, severe cases and deaths caused by P. vivax have remarkably been reported. In contrast to Plasmodium falciparum, which well-known ability to bind to endothelium and placental tissue and form rosettes is related to severity of the disease, it has been a dogma that P. vivax is unable to undergo cytoadherent phenomena. However, some studies have demonstrated that red blood cells (RBCs) infected by P. vivax can cytoadhere to host cells, while the molecules participating in this host-parasite interaction are still a matter of speculation. In the present overview, we address the evidences currently supporting the adhesive profile of P. vivax and, additionally, discuss the putative role of phosphatidylserine-a cell membrane phospholipid with cytoadhesive properties that has been detected on the surface of Plasmodium-parasitized RBCs.

Keywords: Plasmodium vivax; cytoadhesion; eryptosis; phosphatidylserine; rosetting.

Figure 1

Model of phosphatidylserine (PS) role in cytoadhesive phenomena of Plasmodium vivax-parasitized red blood cells (pRBC). Intraerythrocytic parasite development leads to exposure of PS on pRBC surface as a result of suicidal erythrocyte death (eryptosis) induction. In turn, PS mediates sequestration of pRBC to microvasculature through interaction with receptors expressed on endothelial cells, such as CD36, or thrombospondin (TSP) exposed in injured endothelium. In a CD36-dependent manner, PS-exposing pRBC can promote rosetting of non-parasitized red blood cells (RBCs) as well as autoagglutination (clumping) by binding to platelets. Additionally, von Willebrand factor (vWF) can indirectly contribute to the sequestration of PS-exposing pRBC by mediating platelet adhesion at sites of vascular damage (69).