Cerebral malaria is associated with differential cytoadherence to brain endothelial cells.
Janet StormJakob Schmidt JespersenKarl B SeydelTadge SzestakMaurice MbeweNgawina V ChisalaPatricia PhulaChristian W WangTerrie E TaylorChristopher A MoxonThomas LavstsenAlister Gordon CraigPublished in: EMBO molecular medicine (2019)
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.
Keyphrases
- endothelial cells
- plasmodium falciparum
- resting state
- white matter
- cerebral ischemia
- high glucose
- functional connectivity
- vascular endothelial growth factor
- genome wide
- intensive care unit
- emergency department
- multiple sclerosis
- staphylococcus aureus
- copy number
- small molecule
- transcription factor
- cystic fibrosis
- toxoplasma gondii
- protein protein
- amino acid
- cell adhesion