Parasites causing cerebral falciparum malaria bind multiple endothelial receptors and express EPCR and ICAM-1-binding PfEMP1
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Parasites causing cerebral falciparum malaria bind multiple endothelial receptors and express EPCR and ICAM-1-binding PfEMP1. / Tuikue Ndam, Nicaise; Moussiliou, Azizath; Lavstsen, Thomas; Kamaliddin, Claire; Jensen, Anja T R; Mama, Atikatou; Tahar, Rachida; Wang, Christian W; Jespersen, Jakob S; Alao, Jules M; Gamain, Benoit; Theander, Thor G; Deloron, Philippe.
In: The Journal of Infectious Diseases, Vol. 215, No. 12, 2017, p. 1918-1925.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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
Y1 - 2017
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
VL - 215
SP - 1918
EP - 1925
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 12
ER -
ID: 182744776