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Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria

Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by stat...

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Autores principales: Magallón-Tejada, Ariel, Machevo, Sónia, Cisteró, Pau, Lavstsen, Thomas, Aide, Pedro, Rubio, Mercedes, Jiménez, Alfons, Turner, Louise, Valmaseda, Aida, Gupta, Himanshu, De Las Salas, Briegel, Mandomando, Inacio, Wang, Christian W., Petersen, Jens E. V., Muñoz, Jose, Gascón, Joaquim, Macete, Eusebio, Alonso, Pedro L., Chitnis, Chetan E., Bassat, Quique, Mayor, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106025/
https://www.ncbi.nlm.nih.gov/pubmed/27835682
http://dx.doi.org/10.1371/journal.ppat.1006011
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author Magallón-Tejada, Ariel
Machevo, Sónia
Cisteró, Pau
Lavstsen, Thomas
Aide, Pedro
Rubio, Mercedes
Jiménez, Alfons
Turner, Louise
Valmaseda, Aida
Gupta, Himanshu
De Las Salas, Briegel
Mandomando, Inacio
Wang, Christian W.
Petersen, Jens E. V.
Muñoz, Jose
Gascón, Joaquim
Macete, Eusebio
Alonso, Pedro L.
Chitnis, Chetan E.
Bassat, Quique
Mayor, Alfredo
author_facet Magallón-Tejada, Ariel
Machevo, Sónia
Cisteró, Pau
Lavstsen, Thomas
Aide, Pedro
Rubio, Mercedes
Jiménez, Alfons
Turner, Louise
Valmaseda, Aida
Gupta, Himanshu
De Las Salas, Briegel
Mandomando, Inacio
Wang, Christian W.
Petersen, Jens E. V.
Muñoz, Jose
Gascón, Joaquim
Macete, Eusebio
Alonso, Pedro L.
Chitnis, Chetan E.
Bassat, Quique
Mayor, Alfredo
author_sort Magallón-Tejada, Ariel
collection PubMed
description Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7(gC1qR)). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7(gC1qR) overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLβ12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7(gC1qR) and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLβ12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction.
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spelling pubmed-51060252016-12-08 Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria Magallón-Tejada, Ariel Machevo, Sónia Cisteró, Pau Lavstsen, Thomas Aide, Pedro Rubio, Mercedes Jiménez, Alfons Turner, Louise Valmaseda, Aida Gupta, Himanshu De Las Salas, Briegel Mandomando, Inacio Wang, Christian W. Petersen, Jens E. V. Muñoz, Jose Gascón, Joaquim Macete, Eusebio Alonso, Pedro L. Chitnis, Chetan E. Bassat, Quique Mayor, Alfredo PLoS Pathog Research Article Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7(gC1qR)). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7(gC1qR) overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLβ12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7(gC1qR) and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLβ12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction. Public Library of Science 2016-11-11 /pmc/articles/PMC5106025/ /pubmed/27835682 http://dx.doi.org/10.1371/journal.ppat.1006011 Text en © 2016 Magallón-Tejada et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Magallón-Tejada, Ariel
Machevo, Sónia
Cisteró, Pau
Lavstsen, Thomas
Aide, Pedro
Rubio, Mercedes
Jiménez, Alfons
Turner, Louise
Valmaseda, Aida
Gupta, Himanshu
De Las Salas, Briegel
Mandomando, Inacio
Wang, Christian W.
Petersen, Jens E. V.
Muñoz, Jose
Gascón, Joaquim
Macete, Eusebio
Alonso, Pedro L.
Chitnis, Chetan E.
Bassat, Quique
Mayor, Alfredo
Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
title Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
title_full Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
title_fullStr Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
title_full_unstemmed Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
title_short Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
title_sort cytoadhesion to gc1qr through plasmodium falciparum erythrocyte membrane protein 1 in severe malaria
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106025/
https://www.ncbi.nlm.nih.gov/pubmed/27835682
http://dx.doi.org/10.1371/journal.ppat.1006011
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