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Cytoadherence phenotype of Plasmodium falciparum-infected erythrocytes is associated with specific pfemp-1 expression in parasites from children with cerebral malaria.

Almelli T, Ndam NT, Ezimegnon S, Alao MJ, Ahouansou C, Sagbo G, Amoussou A, Deloron P, Tahar R - Malar. J. (2014)

Bottom Line: Parasites from CM patients bind significantly more to CD36 than those from UM patients, but no difference was observed in their binding ability to ICAM-1 and CSPG.CM isolates highly transcribed groups A, B, var2csa, var3, DC8 and DC13 compared to UM parasites.The high transcription levels of var genes belonging to group B positively correlated with increased binding level to CD36.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche pour le Développement (IRD), UMR 216 Mère et Enfant Face aux Infections Tropicales, 4, avenue de l'Observatoire, Paris 75270, France. Rachida.Tahar@ird.fr.

ABSTRACT

Background: Cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) in deep microvasculature endothelia plays a major role in the pathogenesis of cerebral malaria (CM). This biological process is thought to be mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP-1) and human receptors such as CD36 and ICAM-1. The relationship between the expression of PfEMP-1 variants and cytoadherence phenotype in the pathology of malaria is not well established.

Methods: Cytoadherence phenotypes of IEs to CD36, ICAM-1, CSPG and the transcription patterns of A, B, var2csa, var3, var gene groups and domain cassettes DC8 and DC13 were assessed in parasites from children with CM and uncomplicated malaria (UM) to determine if cytoadherence is related to a specific transcription profile of pfemp-1 variants.

Results: Parasites from CM patients bind significantly more to CD36 than those from UM patients, but no difference was observed in their binding ability to ICAM-1 and CSPG. CM isolates highly transcribed groups A, B, var2csa, var3, DC8 and DC13 compared to UM parasites. The high transcription levels of var genes belonging to group B positively correlated with increased binding level to CD36.

Conclusion: CM isolates bind significantly more to CD36 than to ICAM-1, which was correlated with high transcription level of group B var genes, supporting their implication in malaria pathogenesis.

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Related in: MedlinePlus

Transcript abundances ofvargenes from group A, B,var2csaandvar3inPlasmodium falciparumisolates from children presenting with either cerebral (CM) or uncomplicated malaria (UM). Transcript patterns of specific var genes were compared between groups by the Mann-Whitney U test, significant P-values are shown in the figure.
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Fig2: Transcript abundances ofvargenes from group A, B,var2csaandvar3inPlasmodium falciparumisolates from children presenting with either cerebral (CM) or uncomplicated malaria (UM). Transcript patterns of specific var genes were compared between groups by the Mann-Whitney U test, significant P-values are shown in the figure.

Mentions: The transcription level of A, B,var2csa, var3, DC8, and DC13 var genes was analysed by RT-qPCR in 36 UM and 51 CM isolates. Group A, B, var2csa, var3, DC8, and DC13 had significantly higher levels of transcription (P <0.05) in CM isolates than in UM isolates (Table 3, Figures 2 and 3). However, no difference in the transcription level was observed between CM and UM isolates when genes were targeted by A2, DBLγ4/6 and DBLαCIDRα primer sets.Table 3


Cytoadherence phenotype of Plasmodium falciparum-infected erythrocytes is associated with specific pfemp-1 expression in parasites from children with cerebral malaria.

Almelli T, Ndam NT, Ezimegnon S, Alao MJ, Ahouansou C, Sagbo G, Amoussou A, Deloron P, Tahar R - Malar. J. (2014)

Transcript abundances ofvargenes from group A, B,var2csaandvar3inPlasmodium falciparumisolates from children presenting with either cerebral (CM) or uncomplicated malaria (UM). Transcript patterns of specific var genes were compared between groups by the Mann-Whitney U test, significant P-values are shown in the figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150962&req=5

Fig2: Transcript abundances ofvargenes from group A, B,var2csaandvar3inPlasmodium falciparumisolates from children presenting with either cerebral (CM) or uncomplicated malaria (UM). Transcript patterns of specific var genes were compared between groups by the Mann-Whitney U test, significant P-values are shown in the figure.
Mentions: The transcription level of A, B,var2csa, var3, DC8, and DC13 var genes was analysed by RT-qPCR in 36 UM and 51 CM isolates. Group A, B, var2csa, var3, DC8, and DC13 had significantly higher levels of transcription (P <0.05) in CM isolates than in UM isolates (Table 3, Figures 2 and 3). However, no difference in the transcription level was observed between CM and UM isolates when genes were targeted by A2, DBLγ4/6 and DBLαCIDRα primer sets.Table 3

Bottom Line: Parasites from CM patients bind significantly more to CD36 than those from UM patients, but no difference was observed in their binding ability to ICAM-1 and CSPG.CM isolates highly transcribed groups A, B, var2csa, var3, DC8 and DC13 compared to UM parasites.The high transcription levels of var genes belonging to group B positively correlated with increased binding level to CD36.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche pour le Développement (IRD), UMR 216 Mère et Enfant Face aux Infections Tropicales, 4, avenue de l'Observatoire, Paris 75270, France. Rachida.Tahar@ird.fr.

ABSTRACT

Background: Cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) in deep microvasculature endothelia plays a major role in the pathogenesis of cerebral malaria (CM). This biological process is thought to be mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP-1) and human receptors such as CD36 and ICAM-1. The relationship between the expression of PfEMP-1 variants and cytoadherence phenotype in the pathology of malaria is not well established.

Methods: Cytoadherence phenotypes of IEs to CD36, ICAM-1, CSPG and the transcription patterns of A, B, var2csa, var3, var gene groups and domain cassettes DC8 and DC13 were assessed in parasites from children with CM and uncomplicated malaria (UM) to determine if cytoadherence is related to a specific transcription profile of pfemp-1 variants.

Results: Parasites from CM patients bind significantly more to CD36 than those from UM patients, but no difference was observed in their binding ability to ICAM-1 and CSPG. CM isolates highly transcribed groups A, B, var2csa, var3, DC8 and DC13 compared to UM parasites. The high transcription levels of var genes belonging to group B positively correlated with increased binding level to CD36.

Conclusion: CM isolates bind significantly more to CD36 than to ICAM-1, which was correlated with high transcription level of group B var genes, supporting their implication in malaria pathogenesis.

Show MeSH
Related in: MedlinePlus