Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Abstract

Plasmodial species are protozoan parasites that infect erythrocytes. As such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. The hostparasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative agent of the most severe form of malaria, is particularly predisposed to modulating endothelial function through either direct adhesion to endothelial receptor molecules, or by releasing potent host and parasite products that can stimulate endothelial activation and/or disrupt barrier function. In this review, we provide a critical analysis of the current clinical and laboratory evidence for endothelial dysfunction during severe P. falciparum malaria. Future investigations using state-of-the-art technologies such as mass cytometry and organs-on-chips to further delineate parasite-endothelial cell interactions are also discussed.

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

“…PfEMP1-receptor interactions have been shown to activate signalling pathways in endothelial cells (Wu et al, 2011;Gillrie & Ho, 2017), but the effect of these events on pathology is unclear. More recent work has also suggested that as well as cytoadherencemediated events, the accumulation of sequestered IE in vessels may facilitate endothelial dysfunction caused by the local release of soluble mediators following schizont rupture (Gallego-Delgado & Rodriguez, 2017).…”

Rupture and Release: A Role for Soluble Erythrocyte Content in the Pathology of Cerebral Malaria

“…This suggests that the release of intracellular erythrocytic contents triggers endothelial dysfunction. In fact, specific components of the infected erythrocyte have been proposed to contribute to the P. falciparum -induced endothelial disruption, including parasite histones, histidine rich protein II and heme [11]. …”

Risk of aortic dissection in patients with ascending aorta aneurysm: a new biological, morphological, and biomechanical network behind the aortic diameter

“…It has been shown that P. falciparum antigens are present on the surface of infected erythrocytes and bind to the receptors expressed on the VE [72] . After invasion, Plasmodium modulates endothelial function either by direct adhesion to the EC receptors or by releasing parasite products that can induce EC activation, leading to the disruption of the EC barrier [73] . It has also been shown that histones released from merozoites (HeH) stimulate the production of inflammatory mediators by primary human dermal microvascular endothelial cells, supporting the pathogenic role of both host-and pathogen-derived histones in P. falciparum caused malaria [128] .…”