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https://hdl.handle.net/2445/103905
Title: | Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria |
Author: | Magallón Tejada, Ariel Machevo, Sonia Cisteró, Pau Lavstsen, Thomas Aide, Pedro Carlos Paulino Rubio, Mercedes Jiménez, Alfons Turner, Louise Valmaseda, Aida Gupta, Himanshu Salas, Briege de las Mandomando, Inácio Wang, Christian W. Petersen, Jens E. V Muñoz, José Gascón i Brustenga, Joaquim Macete, Eusebio Víctor Alonso, Pedro Chitnis, Chetan E. Bassat Orellana, Quique Mayor Aparicio, Alfredo Gabriel |
Keywords: | Malària Malalties infeccioses Malaria Communicable diseases |
Issue Date: | 11-Nov-2016 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | 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 (Pf3D7gC1qR). 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. Pf3D7gC1qR overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLbeta12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLbeta12 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. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.ppat.1006011 |
It is part of: | PLoS Pathogens, 2016, vol. 12, num. 11, p. e1006011 |
URI: | https://hdl.handle.net/2445/103905 |
Related resource: | http://dx.doi.org/10.1371/journal.ppat.1006011 |
ISSN: | 1553-7366 |
Appears in Collections: | Articles publicats en revistes (ISGlobal) |
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magallon-tejada2016_2291.pdf | 2.17 MB | Adobe PDF | View/Open |
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