Title:
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Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte
Membrane Protein 1 in Severe Malaria
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Author:
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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, Eusébio; Alonso, Pedro; Chitnis, Chetan E.; Bassat Orellana, Quique; Mayor Aparicio, Alfredo Gabriel
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Abstract:
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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. |
Subject(s):
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-Malària -Malalties infeccioses -Malaria -Communicable diseases |
Rights:
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cc by (c) Magallón Tejada, et al., 2016
http://creativecommons.org/licenses/by/3.0/es/ |
Document type:
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Article Article - Published version |
Published by:
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Public Library of Science (PLoS)
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