Open AccessCerebral malaria is associated with differential cytoadherence to brain endothelial cells
Author(s) -
Storm Janet,
Jespersen Jakob S,
Seydel Karl B,
Szestak Tadge,
Mbewe Maurice,
Chisala Ngawina V,
Phula Patricia,
Wang Christian W,
Taylor Terrie E,
Moxon Christopher A,
Lavstsen Thomas,
Craig Alister G
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809164
Subject(s) - malaria , cerebral malaria , plasmodium falciparum , endothelial stem cell , biology , microbiology and biotechnology , blood–brain barrier , immunology , virology , computational biology , neuroscience , genetics , central nervous system , in vitro
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.