Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture

Basim Othman, Leo Zeef, Tadge Szestak, Zineb Rchiad, Janet Storm, Caroline Askonas, Rohit Satyam, Aymen Madkhali, Michael Haley, Simon Wagstaff, Kevin Couper, Arnab Pain, Alister Craig*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants.

Original languageEnglish (US)
Article numbere0295053
JournalPloS one
Volume18
Issue number11 November
DOIs
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
Copyright: © 2023 Othman et al.

ASJC Scopus subject areas

  • General

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