ORCID Profile
0000-0002-7702-1892
Current Organisation
The University of Edinburgh
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Publisher: Public Library of Science (PLoS)
Date: 31-01-2011
Publisher: Public Library of Science (PLoS)
Date: 19-04-2012
Publisher: Proceedings of the National Academy of Sciences
Date: 25-05-2021
Abstract: Mature asexual stages of Plasmodium falciparum -infected erythrocytes (IEs) bind to endothelium to avoid splenic clearance. The PfEMP1 family is the major cytoadhesion ligand at the IE surface and is essential for parasite sequestration. In this study, we show that complement component 1s (C1s), found in serum, cleaves PfEMP1 on the IEs to prevent binding to endothelial cells. We find that the C1s cleavage sites are maintained at semiconserved arginine motifs located at interdomain regions between PfEMP1 receptor-binding domains and upstream of the transmembrane region. This suggests that parasites have taken advantage of a human serum protease, either to escape antibody recognition of sequestered parasites or to d en sequestration and pathogenesis from uncontrolled inflammatory responses threatening host survival.
Publisher: American Society for Microbiology
Date: 08-2006
DOI: 10.1128/IAI.01978-05
Abstract: Determining the ersity of PfEMP1 sequences expressed by Plasmodium falciparum -infected erythrocytes isolated from placentas is important for attempts to develop a pregnancy-specific malaria vaccine. The DBLγ and var2csa DBL3x domains of PfEMP1 molecules are believed to mediate placental sequestration of infected erythrocytes, so the sequences encoding these domains were lified from the cDNAs of placental parasites by using degenerate oligonucleotides. The levels of specific var cDNAs were then determined by quantitative reverse transcription-PCR. Homologues of var2csa DBL3x were the predominant sequences lified from the cDNAs of most placental but not most children's parasites. There was 56% identity between all placental var2csa sequences. Many different DBLγ domains were lified from the cDNAs of placental and children's isolates. var2csa transcripts were the most abundant var transcripts of those tested in 11 of 12 placental isolates and 1 of 6 children's isolates. Gravidity did not affect the levels of var2csa transcripts. We concluded that placental malaria is frequently associated with transcription of var2csa but that other var genes are also expressed, and parasites expressing high levels of var2csa are not restricted to pregnant women. The ersity of var2csa sequences may be important for understanding immunity and for the development of vaccines for malaria during pregnancy.
Publisher: Elsevier BV
Date: 04-2002
Publisher: Oxford University Press (OUP)
Date: 15-04-2002
DOI: 10.1086/339684
Abstract: The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is a highly polymorphic class of variant surface antigens encoded by var genes that play an important role in malaria pathogenesis. This report describes the unexpected finding that 1 of the var genes encoding a PfEMP1 variant that binds to the host receptor chondroitin sulfate A (CSA) and is implicated in malaria in pregnancy is well conserved among P. falciparum isolates worldwide. The N-terminal domains of this PfEMP1 variant are especially highly conserved, whereas the functional CSA binding domain is more variable. Analysis of var gene expression in placental parasites from primigravid women in Malawi did not support a role for this conserved gene in placental infection but identified a second commonly occurring var gene. These results indicate the need for reevaluation of previous assumptions of a minimal overlap between var gene repertoires from different parasite isolates.
Publisher: American Society for Microbiology
Date: 06-2007
DOI: 10.1128/IAI.00249-07
Abstract: The invasion of erythrocytes by Plasmodium falciparum occurs through multiple pathways that can be studied in vitro by examining the invasion of erythrocytes treated with enzymes such as neuraminidase, trypsin, and chymotrypsin. We have studied the invasion pathways used by 31 Kenyan P. falciparum isolates from children with uncomplicated or severe malaria. Six distinct invasion profiles were detected, out of eight possible profiles. The majority of isolates (23 of 31) showed neuraminidase-resistant, trypsin-sensitive invasion, characteristic of the pathway mediated by an unknown parasite ligand and erythrocyte receptor “X.” The neuraminidase-sensitive, trypsin-sensitive phenotype consistent with invasion mediated by the binding of parasite ligand erythrocyte binding antigen 175 to glycophorin A, the most common invasion profile in a previous study of Gambian field isolates, was seen in only 3 of 31 Kenyan isolates. No particular invasion profile was associated with severe P. falciparum malaria, and there was no significant difference in the levels of inhibition by the various enzyme treatments between isolates from children with severe malaria and those from children with uncomplicated malaria ( P , .1 for all enzymes Mann-Whitney U test). These results do not support the hypothesis that differences in invasion phenotypes play an important role in malaria virulence and indicate that considerable gaps remain in our knowledge of the molecular basis of invasion pathways in natural P. falciparum infections.
Publisher: Public Library of Science (PLoS)
Date: 10-04-2012
Publisher: Springer Science and Business Media LLC
Date: 19-03-2021
DOI: 10.1038/S41467-021-21814-Z
Abstract: In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man 5-9 GlcNAc 2 ), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum -infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.
Publisher: Elsevier BV
Date: 10-2006
Publisher: Cold Spring Harbor Laboratory
Date: 27-11-2020
DOI: 10.1101/2020.11.26.399402
Abstract: In both sickle cell disease (SCD) and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man 5-9 GlcNAc 2 ), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. Extravascular haemolysis in SCD correlates with high mannose glycan levels on RBCs. Infection of RBCs with Plasmodium falciparum expose surface mannose N-glycans on healthy RBCs, which occurred at significantly higher levels on RBCs from subjects with sickle cell trait compared to those lacking haemoglobin S. The glycans were associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans, a novel response to cellular stress, is the first molecular mechanism common to both the pathogenesis of SCD and resistance to severe malaria in sickle cell trait.
Publisher: Hindawi Limited
Date: 28-01-2015
DOI: 10.1111/CMI.12403
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alexandra Rowe.