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Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites
Plasmodium falciparum malaria is a deadly pathogen. The invasion of red blood cells (RBCs) by merozoites is a target for vaccine development. Although anti-merozoite antibodies can block invasion in vitro, there is no efficacy in vivo. To explain this discrepancy we hypothesized that complement acti...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972486/ https://www.ncbi.nlm.nih.gov/pubmed/27333049 http://dx.doi.org/10.1016/j.ebiom.2016.05.015 |
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author | Biryukov, Sergei Angov, Evelina Landmesser, Mary E. Spring, Michele D. Ockenhouse, Christian F. Stoute, José A. |
author_facet | Biryukov, Sergei Angov, Evelina Landmesser, Mary E. Spring, Michele D. Ockenhouse, Christian F. Stoute, José A. |
author_sort | Biryukov, Sergei |
collection | PubMed |
description | Plasmodium falciparum malaria is a deadly pathogen. The invasion of red blood cells (RBCs) by merozoites is a target for vaccine development. Although anti-merozoite antibodies can block invasion in vitro, there is no efficacy in vivo. To explain this discrepancy we hypothesized that complement activation could enhance RBC invasion by binding to the complement receptor 1 (CR1). Here we show that a monoclonal antibody directed against the merozoite and human polyclonal IgG from merozoite vaccine recipients enhanced RBC invasion in a complement-dependent manner and that soluble CR1 inhibited this enhancement. Sialic acid-independent strains, that presumably are able to bind to CR1 via a native ligand, showed less complement-dependent enhancement of RBC invasion than sialic acid-dependent strains that do not utilize native CR1 ligands. Confocal fluorescent microscopy revealed that complement-dependent invasion resulted in aggregation of CR1 at the RBC surface in contact with the merozoite. Finally, total anti-P. berghei IgG enhanced parasite growth and C3 deficiency decreased parasite growth in mice. These results demonstrate, contrary to current views, that complement activation in conjunction with antibodies can paradoxically aid parasites invade RBCs and should be considered in future design and testing of merozoite vaccines. |
format | Online Article Text |
id | pubmed-4972486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-49724862016-08-10 Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites Biryukov, Sergei Angov, Evelina Landmesser, Mary E. Spring, Michele D. Ockenhouse, Christian F. Stoute, José A. EBioMedicine Research Paper Plasmodium falciparum malaria is a deadly pathogen. The invasion of red blood cells (RBCs) by merozoites is a target for vaccine development. Although anti-merozoite antibodies can block invasion in vitro, there is no efficacy in vivo. To explain this discrepancy we hypothesized that complement activation could enhance RBC invasion by binding to the complement receptor 1 (CR1). Here we show that a monoclonal antibody directed against the merozoite and human polyclonal IgG from merozoite vaccine recipients enhanced RBC invasion in a complement-dependent manner and that soluble CR1 inhibited this enhancement. Sialic acid-independent strains, that presumably are able to bind to CR1 via a native ligand, showed less complement-dependent enhancement of RBC invasion than sialic acid-dependent strains that do not utilize native CR1 ligands. Confocal fluorescent microscopy revealed that complement-dependent invasion resulted in aggregation of CR1 at the RBC surface in contact with the merozoite. Finally, total anti-P. berghei IgG enhanced parasite growth and C3 deficiency decreased parasite growth in mice. These results demonstrate, contrary to current views, that complement activation in conjunction with antibodies can paradoxically aid parasites invade RBCs and should be considered in future design and testing of merozoite vaccines. Elsevier 2016-05-14 /pmc/articles/PMC4972486/ /pubmed/27333049 http://dx.doi.org/10.1016/j.ebiom.2016.05.015 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Biryukov, Sergei Angov, Evelina Landmesser, Mary E. Spring, Michele D. Ockenhouse, Christian F. Stoute, José A. Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites |
title | Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites |
title_full | Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites |
title_fullStr | Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites |
title_full_unstemmed | Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites |
title_short | Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites |
title_sort | complement and antibody-mediated enhancement of red blood cell invasion and growth of malaria parasites |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972486/ https://www.ncbi.nlm.nih.gov/pubmed/27333049 http://dx.doi.org/10.1016/j.ebiom.2016.05.015 |
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