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Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion
Erythrocyte Binding Antigen of 175 kDa (EBA-175) has a well-defined role in binding to glycophorin A (GpA) during Plasmodium falciparum invasion of erythrocytes. However, EBA-175 is shed post invasion and a role for this shed protein has not been defined. We show that EBA-175 shed from parasites pro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305201/ https://www.ncbi.nlm.nih.gov/pubmed/30556808 http://dx.doi.org/10.7554/eLife.43224 |
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author | Paing, May M Salinas, Nichole D Adams, Yvonne Oksman, Anna Jensen, Anja TR Goldberg, Daniel E Tolia, Niraj H |
author_facet | Paing, May M Salinas, Nichole D Adams, Yvonne Oksman, Anna Jensen, Anja TR Goldberg, Daniel E Tolia, Niraj H |
author_sort | Paing, May M |
collection | PubMed |
description | Erythrocyte Binding Antigen of 175 kDa (EBA-175) has a well-defined role in binding to glycophorin A (GpA) during Plasmodium falciparum invasion of erythrocytes. However, EBA-175 is shed post invasion and a role for this shed protein has not been defined. We show that EBA-175 shed from parasites promotes clustering of RBCs, and EBA-175-dependent clusters occur in parasite culture. Region II of EBA-175 is sufficient for clustering RBCs in a GpA-dependent manner. These clusters are capable of forming under physiological flow conditions and across a range of concentrations. EBA-175-dependent RBC clustering provides daughter merozoites ready access to uninfected RBCs enhancing parasite growth. Clustering provides a general method to protect the invasion machinery from immune recognition and disruption as exemplified by protection from neutralizing antibodies that target AMA-1 and RH5. These findings provide a mechanistic framework for the role of shed proteins in RBC clustering, immune evasion, and malaria. |
format | Online Article Text |
id | pubmed-6305201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63052012018-12-26 Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion Paing, May M Salinas, Nichole D Adams, Yvonne Oksman, Anna Jensen, Anja TR Goldberg, Daniel E Tolia, Niraj H eLife Microbiology and Infectious Disease Erythrocyte Binding Antigen of 175 kDa (EBA-175) has a well-defined role in binding to glycophorin A (GpA) during Plasmodium falciparum invasion of erythrocytes. However, EBA-175 is shed post invasion and a role for this shed protein has not been defined. We show that EBA-175 shed from parasites promotes clustering of RBCs, and EBA-175-dependent clusters occur in parasite culture. Region II of EBA-175 is sufficient for clustering RBCs in a GpA-dependent manner. These clusters are capable of forming under physiological flow conditions and across a range of concentrations. EBA-175-dependent RBC clustering provides daughter merozoites ready access to uninfected RBCs enhancing parasite growth. Clustering provides a general method to protect the invasion machinery from immune recognition and disruption as exemplified by protection from neutralizing antibodies that target AMA-1 and RH5. These findings provide a mechanistic framework for the role of shed proteins in RBC clustering, immune evasion, and malaria. eLife Sciences Publications, Ltd 2018-12-17 /pmc/articles/PMC6305201/ /pubmed/30556808 http://dx.doi.org/10.7554/eLife.43224 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Microbiology and Infectious Disease Paing, May M Salinas, Nichole D Adams, Yvonne Oksman, Anna Jensen, Anja TR Goldberg, Daniel E Tolia, Niraj H Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
title | Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
title_full | Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
title_fullStr | Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
title_full_unstemmed | Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
title_short | Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
title_sort | shed eba-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion |
topic | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305201/ https://www.ncbi.nlm.nih.gov/pubmed/30556808 http://dx.doi.org/10.7554/eLife.43224 |
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