Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C.
Sickle hemoglobin (Hb) S and HbC may protect against malaria by reducing the expression of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of parasitized red blood cells (RBCs), thereby weakening their cytoadherence to microvascular endothelial cells (MVECs) and impai...
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th-mahidol.8242023-03-30T22:48:28Z Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. Beaudry, Jeanette T. Krause, Michael A. Diakite, Seidina A. S. Fay, Michael P. Joshi, Gyan Diakite, Mahamadou White, Nicholas J. Fairhurst, Rick M. Fairhurst, Rick M. Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Diseases Research Unit. Cytoadherence phenotypes Hemoglobins Malian children Plasmodium falciparum Open Access article Sickle hemoglobin (Hb) S and HbC may protect against malaria by reducing the expression of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of parasitized red blood cells (RBCs), thereby weakening their cytoadherence to microvascular endothelial cells (MVECs) and impairing their activation of MVECs to produce pathological responses. Therefore, we hypothesized that parasites causing malaria in HbAS or HbAC heterozygotes have overcome this protective mechanism by expressing PfEMP1 variants which mediate relatively strong binding to MVECs. To test this hypothesis, we performed 31 cytoadherence comparisons between parasites from HbAA and HbAS (or HbAC) Malian children with malaria. Ring-stage parasites from HbAA and HbAS (or HbAC) children were cultivated to trophozoites, purified, and then inoculated in parallel into the same wildtype uninfected RBCs. After one cycle of invasion and maturation to the trophozoite stage expressing PfEMP1, parasite strains were compared for binding to MVECs. In this assay, there were no significant differences in the binding of parasites from HbAS and HbAC children to MVECs compared to those from HbAA children (HbAS, fold-change = 1.46, 95% CI 0.97-2.19, p = 0.07; HbAC, fold-change = 1.19, 95% CI 0.77-1.84, p = 0.43). These data suggest that in-vitro reductions in cytoadherence by HbS and HbC may not be selecting for expression of high-avidity PfEMP1 variants in vivo. Future studies that identify PfEMP1 domains or amino-acid motifs which are selectively expressed in parasites from HbAS children may provide further insights into the mechanism of malaria protection by the sickle-cell trait. 2014-08-01T03:57:35Z 2016-11-01T06:43:33Z 2014-08-01T03:57:35Z 2016-11-01T06:43:33Z 2014-07-31 2014-03-19 Article Beaudry JT, Krause MA, Diakite SA, Fay MP, Joshi G, Diakite M. et al. Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A, S, and C. PLoS One. 2014 Mar 19;9(3):e92185. 10.1371/journal.pone.0092185 1932-6203 (electronic) https://repository.li.mahidol.ac.th/handle/123456789/824 eng Mahidol University PubMed Central application/pdf |
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Cytoadherence phenotypes Hemoglobins Malian children Plasmodium falciparum Open Access article Beaudry, Jeanette T. Krause, Michael A. Diakite, Seidina A. S. Fay, Michael P. Joshi, Gyan Diakite, Mahamadou White, Nicholas J. Fairhurst, Rick M. Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. |
description |
Sickle hemoglobin (Hb) S and HbC may protect against malaria by reducing the
expression of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on
the surface of parasitized red blood cells (RBCs), thereby weakening their
cytoadherence to microvascular endothelial cells (MVECs) and impairing their
activation of MVECs to produce pathological responses. Therefore, we hypothesized
that parasites causing malaria in HbAS or HbAC heterozygotes have overcome this
protective mechanism by expressing PfEMP1 variants which mediate relatively
strong binding to MVECs. To test this hypothesis, we performed 31 cytoadherence
comparisons between parasites from HbAA and HbAS (or HbAC) Malian children with
malaria. Ring-stage parasites from HbAA and HbAS (or HbAC) children were
cultivated to trophozoites, purified, and then inoculated in parallel into the
same wildtype uninfected RBCs. After one cycle of invasion and maturation to the
trophozoite stage expressing PfEMP1, parasite strains were compared for binding
to MVECs. In this assay, there were no significant differences in the binding of
parasites from HbAS and HbAC children to MVECs compared to those from HbAA
children (HbAS, fold-change = 1.46, 95% CI 0.97-2.19, p = 0.07; HbAC,
fold-change = 1.19, 95% CI 0.77-1.84, p = 0.43). These data suggest that
in-vitro reductions in cytoadherence by HbS and HbC may not be selecting for
expression of high-avidity PfEMP1 variants in vivo. Future studies that identify
PfEMP1 domains or amino-acid motifs which are selectively expressed in parasites
from HbAS children may provide further insights into the mechanism of malaria
protection by the sickle-cell trait. |
author2 |
Fairhurst, Rick M. |
author_facet |
Fairhurst, Rick M. Beaudry, Jeanette T. Krause, Michael A. Diakite, Seidina A. S. Fay, Michael P. Joshi, Gyan Diakite, Mahamadou White, Nicholas J. Fairhurst, Rick M. |
format |
Article |
author |
Beaudry, Jeanette T. Krause, Michael A. Diakite, Seidina A. S. Fay, Michael P. Joshi, Gyan Diakite, Mahamadou White, Nicholas J. Fairhurst, Rick M. |
author_sort |
Beaudry, Jeanette T. |
title |
Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. |
title_short |
Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. |
title_full |
Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. |
title_fullStr |
Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. |
title_full_unstemmed |
Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A,S, and C. |
title_sort |
ex-vivo cytoadherence phenotypes of plasmodium falciparum strains from malian children with hemoglobins a,s, and c. |
publishDate |
2014 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/824 |
_version_ |
1763496121060032512 |