Parasites Causing Cerebral Falciparum Malaria Bind Multiple Endothelial Receptors and Express EPCR and ICAM-1-Binding PfEMP1.
J Infect Dis
; 215(12): 1918-1925, 2017 06 15.
Article
en En
| MEDLINE
| ID: mdl-28863469
ABSTRACT
Background:
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the binding and accumulation of infected erythrocytes (IE) to blood vessels and tissues. Specific interactions have been described between PfEMP1 and human endothelial proteins CD36, intercellular adhesion molecule-1 (ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediatric malaria syndromes and the associated PfEMP1 members are still undefined.Methods:
In a cohort of 94 hospitalized children with malaria, we characterized the binding properties of IE collected on admission, and var gene transcription using quantitative polymerase chain reaction.Results:
IE from patients with cerebral malaria were more likely to bind EPCR and ICAM-1 than IE from children with uncomplicated malaria (P = .007). The level of transcripts encoding CIDRα1.4 and CIDRα1.5 domain subclasses was higher in patients with severe disease (P < .05). IE populations exhibiting binding to all 3 receptors had higher levels of transcripts encoding PfEMP1 with CIDRα1.4 and Duffy binding-like (DBL)-ß3 domains than parasites, which only bound CD36.Conclusions:
These results underpin the significance of EPCR binding in pediatric malaria patients that require hospital admission, and support the notion that complementary receptor interactions of EPCR binding PfEMP1with ICAM-1 amplifies development of severe malaria symptoms.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
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Antígenos CD
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Proteínas Protozoarias
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Malaria Falciparum
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Malaria Cerebral
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Receptores de Superficie Celular
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Molécula 1 de Adhesión Intercelular
Límite:
Child, preschool
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Humans
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Infant
Idioma:
En
Revista:
J Infect Dis
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia