Analysis of the Interaction Between Plasmodium falciparum-Infected Erythrocytes and Human Endothelial Cells Using a Laminar Flow System, Bioinformatic Tracking and Transcriptome Analysis

Abstract

During malaria infection, the endothelial lining of the small blood vessels of the brain and other vital organs is strongly stimulated. This leads to fatal complications and poor prognosis of the infection. It is believed that two main reasons are responsible for this pathology, namely the cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) on the one hand and the proinflammatory products released by the IEs which activate the endothelial cells (ECs) on the other hand. Until recently, most of the studies that characterized the activation of ECs were performed under static conditions, which do not reflect the real sequelae in vivo. In this chapter, we present a system, which allows authentic simulation of the IEs-ECs interactions during P. falciparum infection.The main idea of the system is to provide an adequate shear stress over the ECs during the cytoadhesion and stimulation with IEs, which provides a better basis for the investigation of the cytoadhesion pathology through analyzing the ECs' transcriptome after stimulation. On the other hand, analyzing the transcriptome of the IEs might also give deeper analysis of their response to shear stress. Deep understanding of these events might help in the development of novel treatment strategies that interfere with this cell-cell interaction.

Keywords: Cerebral malaria; Cytoadhesion; Endothelial cells; P. falciparum; Shear stress.