Cerebral malaria: role of microparticles and platelets in alterations of the blood–brain barrier

Combes, Valéry; Coltel, Nicolas; Faille, Dorothée; Wassmer, Samuel C.; Grau, Georges E.

doi:10.1016/j.ijpara.2006.02.005

Cited by 124 publications

(109 citation statements)

References 41 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…One of the key pathogenic mechanisms in the virulence of P. falciparum is the phenomenon of cytoadherence, attributed to increased adhesion of infected erythrocytes to blood capillaries [34][35][36][37][38][39][40][41][42] .…”

Section: Discussionmentioning

confidence: 99%

“…In particular, cerebral and placental malaria seem to be dependent on crucial protein-protein interactions that occur between a parasite virulence factors and the endothelial/placental receptors [34][35][36][37][38][39][40][41][42] . The host immune system is hijacked by parasite-derived factors to assist in cytoadherence, for example, by cytokine-induced increased expression of a range of adhesion molecules 16,[18][19][20][21][22][23][24][25] .…”

Section: Discussionmentioning

confidence: 99%

“…Elevated cytokine levels have a variety of physiological effects, generally to the detriment of the hosts 16,[34][35][36][37][38][39][40][41][42] . In fact, malaria as a disease has been looked up on as a manifestation of enhanced pro-inflammatory cytokine production in host 16,[34][35][36][37][38][39][40][41][42] . For example, the clinical manifestations of severe malaria can be correlated with induction of strong pro-inflammatory responses in which plasma levels of circulating TNF-α, IFN-γ and IL-6 increase significantly [19][20][21] .…”

Section: Discussionmentioning

confidence: 99%

“…tration in host tissues, allowing these parasites to avoid splenic clearance which involves degradation and clearing of infected RBCs by the spleen [34][35][36][37][38][39][40] . In severe malaria episodes, an increase in the levels of TNF-α is coupled with enhanced expression of endothelial cell receptors such as ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and E-selectin [34][35][36][37][38][39][40] .…”

mentioning

confidence: 99%

“…In severe malaria episodes, an increase in the levels of TNF-α is coupled with enhanced expression of endothelial cell receptors such as ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and E-selectin [34][35][36][37][38][39][40] . We therefore tested whether recombinant PfTyrRS could modulate expression of endothelial receptors in a static cytoadhesion model assay system.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses

et al. 2011

View full text Add to dashboard Cite

malaria infection triggers pro-inflammatory responses in humans that are detrimental to host health. Parasite-induced enhancement in cytokine levels correlate with malariaassociated pathologies. Here we show that parasite tyrosyl-tRnA synthetase (PfTyrRs), a housekeeping protein translation enzyme, induces pro-inflammatory responses from host immune cells. PfTyrRs exits from the parasite cytoplasm into the infected red blood cell (iRBC) cytoplasm, from where it is released into the extracellular medium on iRBC lysis. using its ELR peptide motif, PfTyrRs specifically binds to and internalizes into host macrophages, leading to enhanced secretion of the pro-inflammatory cytokines TnF-α and IL-6. PfTyrRs-macrophage interaction also augments expression of adherence-linked host endothelial receptors ICAm-1 and VCAm-1. our description of PfTyrRs as a parasite-secreted protein that triggers proinflammatory host responses, along with its atomic resolution crystal structure in complex with tyrosyl-adenylate, provides a novel platform for targeting PfTyrRs in anti-parasitic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses

et al. 2011

View full text Add to dashboard Cite

show abstract

Cerebral Malaria and Neuronal Implications ofPlasmodium FalciparumInfection: From Mechanisms to Advanced Models

2022

View full text Add to dashboard Cite

Reorganization of host red blood cells by the malaria parasite Plasmodium falciparum enables their sequestration via attachment to the microvasculature. This artificially increases the dwelling time of the infected red blood cells within inner organs such as the brain, which can lead to cerebral malaria. Cerebral malaria is the deadliest complication patients infected with P. falciparum can experience and still remains a major public health concern despite effective antimalarial therapies. Here, the current understanding of the effect of P. falciparum cytoadherence and their secreted proteins on structural features of the human blood-brain barrier and their involvement in the pathogenesis of cerebral malaria are highlighted. Advanced 2D and 3D in vitro models are further assessed to study this devastating interaction between parasite and host. A better understanding of the molecular mechanisms leading to neuronal and cognitive deficits in cerebral malaria will be pivotal in devising new strategies to treat and prevent blood-brain barrier dysfunction and subsequent neurological damage in patients with cerebral malaria. MalariaMalaria is an ancient mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. According to the latest World Malaria Report published by the World Health

show abstract

Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding

Kavian

Marut

Servettaz

et al. 2015

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc.Methods. First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage.Results. In vitro, pantethine inhibited MP shedding from tumor necrosis factor-stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1.Conclusion. Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc.

show abstract

Cerebral malaria: role of microparticles and platelets in alterations of the blood–brain barrier

Cited by 124 publications

References 41 publications

Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses

Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses

Cerebral Malaria and Neuronal Implications ofPlasmodium FalciparumInfection: From Mechanisms to Advanced Models

Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding

Contact Info

Product

Resources

About