Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

Janet Storm; Jakob S. Jespersen; Karl B. Seydel; Tadge Szestak; Maurice Mbewe; Ngawina V. Chisala; Patricia Phula; Christian W. Wang; Terrie E. Taylor; Christopher A. Moxon; Thomas Lavstsen; Alister G. Craig

doi:10.15252/emmm.201809164

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

Janet Storm^*, Jakob S. Jespersen, Karl B. Seydel, Tadge Szestak, Maurice Mbewe, Ngawina V. Chisala, Patricia Phula, Christian W. Wang, Terrie E. Taylor, Christopher A. Moxon, Thomas Lavstsen, Alister G. Craig

^*Corresponding author for this work

DISCOVERY team

29 Citations (Scopus)

43 Downloads (Pure)

Abstract

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.

Original language	English
Article number	e9164
Journal	EMBO Molecular Medicine
Volume	2019
Issue number	11
Number of pages	15
ISSN	1757-4676
DOIs	https://doi.org/10.15252/emmm.201809164
Publication status	Published - 1 Feb 2019

Keywords

cerebral malaria
cytoadherence
paediatric patient isolates
PfEMP1
Plasmodium falciparum

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.15252/emmm.201809164Licence: CC BY

Cerebral malaria is associated with differential cytoadherence to brain endothelial cellsFinal published version, 511 KBLicence: CC BY

Cite this

@article{bfa11531c4c245bbbf1530a5eb694554,

title = "Cerebral malaria is associated with differential cytoadherence to brain endothelial cells",

abstract = "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.",

keywords = "cerebral malaria, cytoadherence, paediatric patient isolates, PfEMP1, Plasmodium falciparum",

author = "Janet Storm and Jespersen, {Jakob S.} and Seydel, {Karl B.} and Tadge Szestak and Maurice Mbewe and Chisala, {Ngawina V.} and Patricia Phula and Wang, {Christian W.} and Taylor, {Terrie E.} and Moxon, {Christopher A.} and Thomas Lavstsen and Craig, {Alister G.}",

year = "2019",

month = feb,

day = "1",

doi = "10.15252/emmm.201809164",

language = "English",

volume = "2019",

journal = "EMBO Molecular Medicine",

issn = "1757-4676",

publisher = "Wiley-Blackwell",

number = "11",

}

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 -

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this