Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

TY - JOUR

T1 - Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

AU - Storm, Janet

AU - Jespersen, Jakob S.

AU - Seydel, Karl B.

AU - Szestak, Tadge

AU - Mbewe, Maurice

AU - Chisala, Ngawina V.

AU - Phula, Patricia

AU - Wang, Christian W.

AU - Taylor, Terrie E.

AU - Moxon, Christopher A.

AU - Lavstsen, Thomas

AU - Craig, Alister G.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Sequestration of Plasmodium falciparum-infected erythrocytes (IE) within the brain microvasculature is a hallmark of cerebral malaria (CM). Using a microchannel flow adhesion assay with TNF-activated primary human microvascular endothelial cells, we demonstrate that IE isolated from Malawian paediatric CM cases showed increased binding to brain microvascular endothelial cells compared to IE from uncomplicated malaria (UM) cases. Further, UM isolates showed significantly greater adhesion to dermal than to brain microvascular endothelial cells. The major mediator of parasite adhesion is P. falciparum erythrocyte membrane protein 1, encoded by var genes. Higher levels of var gene transcripts predicted to bind host endothelial protein C receptor (EPCR) and ICAM-1 were detected in CM isolates. These data provide further evidence for differential tissue binding in severe and uncomplicated malaria syndromes, and give additional support to the hypothesis that CM pathology is based on increased cytoadherence of IE in the brain microvasculature.

AB - Sequestration of Plasmodium falciparum-infected erythrocytes (IE) within the brain microvasculature is a hallmark of cerebral malaria (CM). Using a microchannel flow adhesion assay with TNF-activated primary human microvascular endothelial cells, we demonstrate that IE isolated from Malawian paediatric CM cases showed increased binding to brain microvascular endothelial cells compared to IE from uncomplicated malaria (UM) cases. Further, UM isolates showed significantly greater adhesion to dermal than to brain microvascular endothelial cells. The major mediator of parasite adhesion is P. falciparum erythrocyte membrane protein 1, encoded by var genes. Higher levels of var gene transcripts predicted to bind host endothelial protein C receptor (EPCR) and ICAM-1 were detected in CM isolates. These data provide further evidence for differential tissue binding in severe and uncomplicated malaria syndromes, and give additional support to the hypothesis that CM pathology is based on increased cytoadherence of IE in the brain microvasculature.

KW - cerebral malaria

KW - cytoadherence

KW - paediatric patient isolates

KW - PfEMP1

KW - Plasmodium falciparum

U2 - 10.15252/emmm.201809164

DO - 10.15252/emmm.201809164

M3 - Journal article

C2 - 30610112

AN - SCOPUS:85059522343

SN - 1757-4676

VL - 2019

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

IS - 11

M1 - e9164

ER -