ArticleThe Journal of experimental medicine2021
Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood-brain barrier in cerebral malaria.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 96 citations in OpenAlex.
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- Beyond the mouse: organoids, spheroids, and organs-on-chips as the (inevitable) future of malaria research?Malaria journal · 2026Review
- Cerebral malaria in resource-limited African regions: Diagnostic and therapeutic challenges.Infectious medicine · 2026Review
- Anti-GPI scFv as a Promising Tool for Intervention Against Cerebral Malaria in Mice.International journal of molecular sciences · 2026Article
- Article
- Methylene blue treatment of fatal cerebral malaria and identification of potential blood biomarkers.Nature communications · 2025Article
- A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria.Scientific reports · 2025Article
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- ICAM-1/CD18-mediated sequestration of parasitized phagocytes in cortical capillaries promotes neuronal colonization by Toxoplasma gondii.Nature communications · 2025Article
- Brain endothelial cells as phagocytes: mechanisms and implications.Fluids and barriers of the CNS · 2025Review
- Evasive mechanisms of human VSG and PfEMP1 antigens with link to Vaccine scenario: a review.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- Breaking the bind: PfEMP1-specific antibodies in cerebral malaria.Frontiers in immunology · 2025Review
- A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children.BMC medicine · 2024Article
- Transcriptional responses of brain endothelium toMicrobiology spectrum · 2024Article
- Plasmodium vivax tryptophan-rich antigen reduces type I collagen secretion via the NF-κBp65 pathway in splenic fibroblasts.Parasites & vectors · 2024Article
- A human pluripotent stem cell-derived in vitro model of the blood-brain barrier in cerebral malaria.Fluids and barriers of the CNS · 2024Article
- Beyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria.Nature communications · 2024Article
- Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.Trends in parasitology · 2024Review
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Review
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12 authors at 4 institutions in 4 countries.
Funding
Abstract
Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum-infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling. We have previously linked dual intercellular adhesion molecule-1 (ICAM-1)- and endothelial protein C receptor (EPCR)-binding P. falciparum parasites to these symptoms, but the mechanism driving the pathogenesis has not been identified. Here, we used a 3D spheroid model of the blood-brain barrier (BBB) to determine unexpected new features of IEs expressing the dual-receptor binding PfEMP1 parasite proteins. Analysis of multiple parasite lines shows that IEs are taken up by brain endothelial cells in an ICAM-1-dependent manner, resulting in breakdown of the BBB and swelling of the endothelial cells. Via ex vivo analysis of postmortem tissue samples from CM patients, we confirmed the presence of parasites within brain endothelial cells. Importantly, this discovery points to parasite ingress into the brain endothelium as a contributing factor to the pathology of human CM.
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