Parasites causing cerebral falciparum malaria bind multiple endothelial receptors and express EPCR and ICAM-1-binding PfEMP1

TY - JOUR

T1 - Parasites causing cerebral falciparum malaria bind multiple endothelial receptors and express EPCR and ICAM-1-binding PfEMP1

AU - Tuikue Ndam, Nicaise

AU - Moussiliou, Azizath

AU - Lavstsen, Thomas

AU - Kamaliddin, Claire

AU - Jensen, Anja T R

AU - Mama, Atikatou

AU - Tahar, Rachida

AU - Wang, Christian W

AU - Jespersen, Jakob S

AU - Alao, Jules M

AU - Gamain, Benoit

AU - Theander, Thor G

AU - Deloron, Philippe

PY - 2017/6/15

Y1 - 2017/6/15

N2 - 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)-β3 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.

AB - 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)-β3 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.

U2 - 10.1093/infdis/jix230

DO - 10.1093/infdis/jix230

M3 - Journal article

C2 - 28863469

SN - 0022-1899

VL - 215

SP - 1918

EP - 1925

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 12

ER -