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Alexandra J Rowe - One of the best experts on this subject based on the ideXlab platform.
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a human Complement Receptor 1 polymorphism that reduces plasmodium falciparum rosetting confers protection against severe malaria
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Ian A Cockburn, Joann M Moulds, John C Reeder, Moses Baisor, Stephen J. Allen, A Odonnell, Moses J. Bockarie, Margaret J Mackinnon, Alexandra J RoweAbstract:Parasitized red blood cells (RBCs) from children suffering from severe malaria often adhere to Complement Receptor 1 (CR1) on uninfected RBCs to form clumps of cells known as “rosettes.” Despite a well documented association between rosetting and severe malaria, it is controversial whether rosetting is a cause or a correlate of parasite virulence. CR1-deficient RBC show greatly reduced rosetting; therefore, we hypothesized that, if rosetting is a direct cause of malaria pathology, CR1-deficient individuals should be protected against severe disease. In this study, we show that RBC CR1 deficiency occurs in up to 80% of healthy individuals from the malaria-endemic regions of Papua New Guinea. This RBC CR1 deficiency is associated with polymorphisms in the CR1 gene and, unexpectedly, with α-thalassemia, a common genetic disorder in Melanesian populations. Analysis of a case-control study demonstrated that the CR1 polymorphisms and α-thalassemia independently confer protection against severe malaria. We have therefore identified CR1 as a new malaria resistance gene and provided compelling evidence that rosetting is an important parasite virulence phenotype that should be a target for drug and vaccine development.
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p falciparum rosetting mediated by a parasite variant erythrocyte membrane protein and Complement Receptor 1
Nature, 1997Co-Authors: Alexandra J Rowe, Joann M Moulds, Chris I. Newbold, Louis H MillerAbstract:P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and Complement-Receptor 1
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p falciparum rosetting mediated by a parasite variant erythrocyte membrane protein and Complement Receptor 1
Nature, 1997Co-Authors: Alexandra J Rowe, Joann M Moulds, Chris I. Newbold, Louis H MillerAbstract:The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence1. Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes2,3,4,5. The molecular basis of rosetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands6. Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1 (refs 7, 8), which is encoded by the var gene family9,10,11. Here we report that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1, encoded by a specific var gene. We also report that Complement-Receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (Sl(a−))12 have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria.
Joann M Moulds - One of the best experts on this subject based on the ideXlab platform.
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Complement Receptor 1 polymorphisms associated with resistance to severe malaria in Kenya.
Malaria Journal, 2005Co-Authors: Vandana Thathy, Joann M Moulds, Walter Otieno, Bernard Guyah, Jose A StouteAbstract:Background It has been hypothesized that the African alleles Sl2 and McCbof the Swain-Langley (Sl) and McCoy (McC) blood group antigens of the Complement Receptor 1 (CR1) may confer a survival advantage in the setting of Plasmodium falciparum malaria, but this has not been demonstrated.
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Complement Receptor 1 polymorphisms associated with resistance to severe malaria in Kenya
Malaria Journal, 2005Co-Authors: Vandana Thathy, Joann M Moulds, Walter Otieno, Bernard Guyah, Jose A StouteAbstract:Background It has been hypothesized that the African alleles Sl2 and McC ^ b of the Swain-Langley (Sl) and McCoy (McC) blood group antigens of the Complement Receptor 1 (CR1) may confer a survival advantage in the setting of Plasmodium falciparum malaria, but this has not been demonstrated. Methods To test this hypothesis, children in western Kenya with severe malaria-associated anaemia or cerebral malaria were matched to symptomatic uncomplicated malaria controls by age and gender. Swain-Langley and McCoy blood group alleles were determined by restriction fragment length polymorphism and conditional logistic regression was carried out. Results No significant association was found between the African alleles and severe malaria-associated anaemia. However, children with Sl2/2 genotype were less likely to have cerebral malaria (OR = 0.17, 95% CI 0.04 to 0.72, P = 0.02) than children with Sl1/1 . In particular, individuals with Sl2/2 McC ^ a/b genotype were less likely to have cerebral malaria (OR = 0.18, 95% CI 0.04 to 0.77, P = 0.02) than individuals with Sl1/1 McC ^ a/a . Conclusion These results support the hypothesis that the Sl2 allele and, possibly, the McC ^ b allele evolved in the context of malaria transmission and that in certain combinations probably confer a survival advantage on these populations.
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a human Complement Receptor 1 polymorphism that reduces plasmodium falciparum rosetting confers protection against severe malaria
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Ian A Cockburn, Joann M Moulds, John C Reeder, Moses Baisor, Stephen J. Allen, A Odonnell, Moses J. Bockarie, Margaret J Mackinnon, Alexandra J RoweAbstract:Parasitized red blood cells (RBCs) from children suffering from severe malaria often adhere to Complement Receptor 1 (CR1) on uninfected RBCs to form clumps of cells known as “rosettes.” Despite a well documented association between rosetting and severe malaria, it is controversial whether rosetting is a cause or a correlate of parasite virulence. CR1-deficient RBC show greatly reduced rosetting; therefore, we hypothesized that, if rosetting is a direct cause of malaria pathology, CR1-deficient individuals should be protected against severe disease. In this study, we show that RBC CR1 deficiency occurs in up to 80% of healthy individuals from the malaria-endemic regions of Papua New Guinea. This RBC CR1 deficiency is associated with polymorphisms in the CR1 gene and, unexpectedly, with α-thalassemia, a common genetic disorder in Melanesian populations. Analysis of a case-control study demonstrated that the CR1 polymorphisms and α-thalassemia independently confer protection against severe malaria. We have therefore identified CR1 as a new malaria resistance gene and provided compelling evidence that rosetting is an important parasite virulence phenotype that should be a target for drug and vaccine development.
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p falciparum rosetting mediated by a parasite variant erythrocyte membrane protein and Complement Receptor 1
Nature, 1997Co-Authors: Alexandra J Rowe, Joann M Moulds, Chris I. Newbold, Louis H MillerAbstract:P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and Complement-Receptor 1
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p falciparum rosetting mediated by a parasite variant erythrocyte membrane protein and Complement Receptor 1
Nature, 1997Co-Authors: Alexandra J Rowe, Joann M Moulds, Chris I. Newbold, Louis H MillerAbstract:The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence1. Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes2,3,4,5. The molecular basis of rosetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands6. Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1 (refs 7, 8), which is encoded by the var gene family9,10,11. Here we report that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1, encoded by a specific var gene. We also report that Complement-Receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (Sl(a−))12 have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria.
Surendra K Prajapati - One of the best experts on this subject based on the ideXlab platform.
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Complement Receptor 1 availability on red blood cell surface modulates plasmodium vivax invasion of human reticulocytes
Scientific Reports, 2019Co-Authors: Surendra K Prajapati, Celine Borlon, Eduard Roviravallbona, Jakub Gruszczyk, Sebastien Menant, Waihong Tham, Johanna Helena Kattenberg, Elizabeth VillasisAbstract:Plasmodium vivax parasites preferentially invade reticulocyte cells in a multistep process that is still poorly understood. In this study, we used ex vivo invasion assays and population genetic analyses to investigate the involvement of Complement Receptor 1 (CR1) in P. vivax invasion. First, we observed that P. vivax invasion of reticulocytes was consistently reduced when CR1 surface expression was reduced through enzymatic cleavage, in the presence of naturally low-CR1-expressing cells compared with high-CR1-expressing cells, and with the addition of soluble CR1, a known inhibitor of P. falciparum invasion. Immuno-precipitation experiments with P. vivax Reticulocyte Binding Proteins showed no evidence of complex formation. In addition, analysis of CR1 genetic data for worldwide human populations with different exposure to malaria parasites show significantly higher frequency of CR1 alleles associated with low Receptor expression on the surface of RBCs and higher linkage disequilibrium in human populations exposed to P. vivax malaria compared with unexposed populations. These results are consistent with a positive selection of low-CR1-expressing alleles in vivax-endemic areas. Collectively, our findings demonstrate that CR1 availability on the surface of RBCs modulates P. vivax invasion. The identification of new molecular interactions is crucial to guiding the rational development of new therapeutic interventions against vivax malaria.
Louis H Miller - One of the best experts on this subject based on the ideXlab platform.
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p falciparum rosetting mediated by a parasite variant erythrocyte membrane protein and Complement Receptor 1
Nature, 1997Co-Authors: Alexandra J Rowe, Joann M Moulds, Chris I. Newbold, Louis H MillerAbstract:P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and Complement-Receptor 1
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p falciparum rosetting mediated by a parasite variant erythrocyte membrane protein and Complement Receptor 1
Nature, 1997Co-Authors: Alexandra J Rowe, Joann M Moulds, Chris I. Newbold, Louis H MillerAbstract:The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence1. Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes2,3,4,5. The molecular basis of rosetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands6. Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1 (refs 7, 8), which is encoded by the var gene family9,10,11. Here we report that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1, encoded by a specific var gene. We also report that Complement-Receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (Sl(a−))12 have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria.
Elizabeth Villasis - One of the best experts on this subject based on the ideXlab platform.
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Complement Receptor 1 availability on red blood cell surface modulates plasmodium vivax invasion of human reticulocytes
Scientific Reports, 2019Co-Authors: Surendra K Prajapati, Celine Borlon, Eduard Roviravallbona, Jakub Gruszczyk, Sebastien Menant, Waihong Tham, Johanna Helena Kattenberg, Elizabeth VillasisAbstract:Plasmodium vivax parasites preferentially invade reticulocyte cells in a multistep process that is still poorly understood. In this study, we used ex vivo invasion assays and population genetic analyses to investigate the involvement of Complement Receptor 1 (CR1) in P. vivax invasion. First, we observed that P. vivax invasion of reticulocytes was consistently reduced when CR1 surface expression was reduced through enzymatic cleavage, in the presence of naturally low-CR1-expressing cells compared with high-CR1-expressing cells, and with the addition of soluble CR1, a known inhibitor of P. falciparum invasion. Immuno-precipitation experiments with P. vivax Reticulocyte Binding Proteins showed no evidence of complex formation. In addition, analysis of CR1 genetic data for worldwide human populations with different exposure to malaria parasites show significantly higher frequency of CR1 alleles associated with low Receptor expression on the surface of RBCs and higher linkage disequilibrium in human populations exposed to P. vivax malaria compared with unexposed populations. These results are consistent with a positive selection of low-CR1-expressing alleles in vivax-endemic areas. Collectively, our findings demonstrate that CR1 availability on the surface of RBCs modulates P. vivax invasion. The identification of new molecular interactions is crucial to guiding the rational development of new therapeutic interventions against vivax malaria.