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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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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. |
format | Online Article Text |
id | pubmed-5106025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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