Characterization of tissue tropism in Plasmodium falciparum malaria

Abstract

Cytoadhesion and sequestration of Plasmodium falciparum Infected Erythrocytes (IEs) are the key modes of parasite virulence. Var gene family produces a diverse repertoire of PfEMP1 proteins, which are transported to the IE surface, and interact specifically with the human endothelial receptors, leading to multiple organ complications in severe malaria. Tissue tropism is the ability of a pathogen to invade a tissue or an organ in a specific manner. P. falciparum is well recognized for its ability to sequester in the deep microvasculature of vital organs such as kidneys, lungs, hearts, and gastrointestinal tract, but the tissue tropism in malaria is not well understood. To investigate the host-parasite interactions at the vascular endothelia, we have performed static cytoadherence assays with the primary human brain endothelial cell line (HBEC-5i). Specific binding was observed with the P. falciparum-infected RBCs to the brain endothelial cell line. To learn more about the interaction specificity of the PFEMP1 proteins for the endothelial receptors, in order to unleash the tissue tropism exhibited by the parasite, we searched for the human endothelial receptors expressed across different tissues and associated with cytoadhesion. We have overexpressed some of them in the HEK293T cell line. PF3D7_0420900, a PfEMP1 protein from the var subgroup B has been observed to be enriched in the CD151 adhered IEs. It could be a potential interacting partner of CD151. Cytoadhesion assays with the rest of the endothelial receptors followed by RNA sequencing of the adhered IEs would reveal the PfEMP1 specificity. This study would pave the way for therapeutic research and help in controlling the spread of malaria.