ArticlemBio2022
Plasmodium falciparum and TNF-α Differentially Regulate Inflammatory and Barrier Integrity Pathways in Human Brain Endothelial Cells.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Plasmodium-induced disruption of brain endothelial barrier integrity in vitro and in mice is prevented by inhibitors of farnesyltransferase.Malaria journal · 2026Article
- Article
- Article
- Mechanisms of parasite-mediated disruption of brain vessels.FEBS letters · 2026Review
- Betanin, a Natural Product from Red Beets, Improves Endothelial Dysfunction through Activation of Autophagy.Current medicinal chemistry · 2026Article
- β-Dystroglycan Downregulation and Astrocytic Alterations: A Possible Role in Blood-Brain Barrier Disruption During Experimental Cerebral Malaria.Molecular neurobiology · 2025Article
- Prolonged dysregulation of gene expression and biomarkers of coagulation, fibrinolysis, and endothelium in pediatric central nervous system malaria.BMC infectious diseases · 2025Article
- Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.EMBO molecular medicine · 2025Article
- Dengue virus NS1 protein does not activate TLR4 and has a modest effect on endothelial monolayer integrity compared to TNF.PLoS pathogens · 2025Article
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- The intersection of influenza infection and autoimmunity.Frontiers in immunology · 2025Review
- Transcriptional responses of brain endothelium toMicrobiology spectrum · 2024Article
- Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis.Trends in parasitology · 2024Review
- Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.JCI insight · 2023Article
- Probing cerebral malaria inflammation in 3D human brain microvessels.Cell reports · 2023Article
- Vitamin C-rich juice co-administration with artemether-lumefantrine ameliorates oxido-inflammatory responses in Plasmodium berghei-infected mice.Parasitology research · 2023Article
- Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.PloS one · 2023Article
- Endothelial type I interferon response and brain diseases: identifying STING as a therapeutic target.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cerebral malaria is a severe complication of Plasmodium falciparum infection characterized by the loss of blood-brain barrier (BBB) integrity, which is associated with brain swelling and mortality in patients. P. falciparum-infected red blood cells and inflammatory cytokines, like tumor necrosis factor alpha (TNF-α), have been implicated in the development of cerebral malaria, but it is still unclear how they contribute to the loss of BBB integrity. Here, a combination of transcriptomic analysis and cellular assays detecting changes in barrier integrity and endothelial activation were used to distinguish between the effects of P. falciparum and TNF-α on a human brain microvascular endothelial cell (HBMEC) line and in primary human brain microvascular endothelial cells. We observed that while TNF-α induced high levels of endothelial activation, it only caused a small increase in HBMEC permeability. Conversely, P. falciparum-infected red blood cells (iRBCs) led to a strong increase in HBMEC permeability that was not mediated by cell death. Distinct transcriptomic profiles of TNF-α and P. falciparum in HBMECs confirm the differential effects of these stimuli, with the parasite preferentially inducing an endoplasmic reticulum stress response. Our results establish that there are fundamental differences in the responses induced by TNF-α and P. falciparum on brain endothelial cells and suggest that parasite-induced signaling is a major component driving the disruption of the BBB during cerebral malaria, proposing a potential target for much needed therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.