Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

Jambou, Ronan; Combes, Valéry; Jambou, Marie-Jose; Weksler, Babeth B.; Couraud, Pierre‐Olivier; Grau, Georges E.

doi:10.1371/journal.ppat.1001021

Cited by 95 publications

(87 citation statements)

References 66 publications

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“…128 Endothelial permeability in bone marrow endothelial cells was augmented by the transfer of EV containing RNA-induced silencing complex (RISC) proteins, including the Argonaut protein Ago2. The findings are consistent with the reported occurrence of trogocytosis, 62 and the contact-dependent but cytoadherence-independent activation of endothelial cells by intact IRBC. Parasite-derived proteins are also contained within EV, 129,130 so that there may be intracellular delivery of parasite products to endothelial cells.…”

supporting

confidence: 92%

“…61 Interestingly, IRBC adhesion to ICAM-1 on a brain endothelial cell line (hCMEC/D3) has been linked to the formation of endothelial cup-like structures and trogocytosis of membrane fragments of IRBC, and the processes are associated with disruption of barrier integrity. 62 As endothelial docking structures or transmigrating cups are well described during leukocyte transmigration, 63 their formation around adherent IRBC that do not transmigrate is somewhat surprising. Moreover, transmigrating cups around neutrophils has been shown to be a mechanism for the maintenance rather than disruption of barrier function.…”

Section: Cytoadherencementioning

confidence: 99%

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Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Gillrie

2016

Tissue Barriers

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Plasmodial species are protozoan parasites that infect erythrocytes. As such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. The hostparasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative agent of the most severe form of malaria, is particularly predisposed to modulating endothelial function through either direct adhesion to endothelial receptor molecules, or by releasing potent host and parasite products that can stimulate endothelial activation and/or disrupt barrier function. In this review, we provide a critical analysis of the current clinical and laboratory evidence for endothelial dysfunction during severe P. falciparum malaria. Future investigations using state-of-the-art technologies such as mass cytometry and organs-on-chips to further delineate parasite-endothelial cell interactions are also discussed.

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supporting

confidence: 92%

Section: Cytoadherencementioning

confidence: 99%

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Gillrie

2016

Tissue Barriers

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“…Signal transduction for amebic trogocytosis and phagocytosis are mediated by PI3K and C2-domaincontaining protein kinase (C2PK) for actin polymerization; however Eh trogocytosis is prevalent in living cells. The transfer of materials from the Plasmodium falciparum-infected red blood cells (IRBC) to the brain endothelial cells (ECs) plasma membrane in a trogocytosislike process, resulting in the transformation of EC into a target for the cytotoxic T cells and contributing to peri-vascular oedema and cerebral malaria (CM) [80]. The process of intercellular exchange, trogocytosis is an evolutionarily conserved process, benefits some pathogens by enhancing dissemination early during infection, and improves our understanding of how this process impacts CM.…”

Section: Perforin/ Granzyme Pathwaymentioning

confidence: 99%

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

El‐Ashram¹,

Mehmood²,

Dinçel³

et al. 2017

Integr Mol Med

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The rich repertoire of cell death events is a crucial biological process that deserves extensive review at a formative time for the development of our knowledge concerning the state-of-the-art data on their cellular and molecular mechanisms of action and the ways in which they can be manipulated in and by protozoan parasites. We have attempted to provide a comprehensive overview to reveal intervention points that could be exploited to discover novel therapies, vaccine strategies and prophylactic intervention points for protozoan parasites, and to understand the parasitic disease progression and the infection consequence.

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“…Most of the molecules implicated in the adhesion of iRBC on endothelial cells (ECs) are already described; however, the structure of the iRBC/EC junction and the impact of this adhesion on the EC are poorly understood. 6 To this end, Jambou and colleagues demonstrated the transfer of material from the iRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced iRBC engulfing process. The transfer of iRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular edema, associated with CM.…”

Section: Introductionmentioning

confidence: 99%

Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria

Canavese

Spaccapelo

2014

Pathogens and Global Health

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Cerebral malaria (CM) is the major lethal complication of Plasmodium falciparum infection. It is characterized by persistent coma along with symmetrical motor signs. Several clinical, histopathological, and laboratory studies have suggested that cytoadherence of parasitized erythrocytes, neural injury by malarial toxin, and excessive inflammatory cytokine production are possible pathogenic mechanisms. Although the detailed pathophysiology of CM remains unsolved, it is thought that the binding of parasitized erythrocytes to the cerebral endothelia of microvessels, leading to their occlusion and the consequent angiogenic dysregulation play a key role in the disease pathogenesis. Recent evidences showed that vascular endothelial growth factor (VEGF) and its receptor-related molecules are over-expressed in the brain tissues of CM patients, as well as increased levels of VEGF are detectable in biologic samples from malaria patients. Whether the modulation of VEGF is causative agent of CM mortality or a specific phenotype of patients with susceptibility to fatal CM needs further evaluation. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review and discuss here what it is currently known in regard to the role of VEGF in CM as well as VEGF as a potential biomarker.

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Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

Cited by 95 publications

References 66 publications

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria

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