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Analysis of Erythrocyte Invasion Mechanisms of Plasmodium falciparum Clinical Isolates Across 3 Malaria-Endemic Areas in Ghana.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2015 Oct 15; Vol. 212 (8), pp. 1288-97. Date of Electronic Publication: 2015 Apr 02. - Publication Year :
- 2015
-
Abstract
- Background: Plasmodium falciparum invades human erythrocytes by using an array of ligands that interact with several receptors, including sialic acid (SA), complement receptor 1 (CR1), and basigin. We hypothesized that in malaria-endemic areas, parasites vary invasion pathways under immune pressure. Therefore, invasion mechanisms of clinical isolates collected from 3 zones of Ghana with different levels of endemicity (from lowest to highest, Accra, Navrongo, and Kintampo) were compared using standardized methods.<br />Methods: Blood samples were collected from children aged 2-14 years in whom malaria was diagnosed, and erythrocyte invasion phenotypes were determined using the enzymes neuraminidase, chymotrypsin, and trypsin, which differentially cleave receptors from the erythrocyte surface. In addition, antibodies against CR1 and basigin were used to determine the contributions of these receptors to invasion. Gene expression levels of P. falciparum invasion ligands were also examined.<br />Results: The parasites generally expressed SA-independent invasion phenotypes across the malaria-endemic areas, with parasites from Kintampo showing the highest invasion rates in neuraminidase-treated erythrocytes. CR1 was a major mediator of SA-independent invasion, while basigin was essential for both SA-dependent and SA-independent invasion mechanisms. Furthermore, expression of the basigin ligand PfRh5 was the best predictor of donor parasitemia.<br />Conclusions: Erythrocyte invasion phenotypes expressed by P. falciparum are influenced by endemicity levels, and the PfRh5-basigin pathway is a potential vaccine target.<br /> (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Adolescent
Basigin immunology
Child
Child, Preschool
Female
Ghana epidemiology
Humans
Malaria, Falciparum epidemiology
Malaria, Falciparum parasitology
Male
Neuraminidase immunology
Neuraminidase metabolism
Parasitemia
Plasmodium falciparum genetics
Receptors, Complement 3b immunology
Carrier Proteins immunology
Endemic Diseases
Erythrocytes parasitology
Malaria, Falciparum immunology
N-Acetylneuraminic Acid immunology
Plasmodium falciparum immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 212
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 25838264
- Full Text :
- https://doi.org/10.1093/infdis/jiv207