Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Paing, May M, Salinas, Nichole D, Adams, Yvonne, Oksman, Anna, Jensen, Anja TR, Goldberg, Daniel E, Tolia, Niraj H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
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
_version_ 1783382513016635392
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
work_keys_str_mv AT paingmaym shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion
AT salinasnicholed shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion
AT adamsyvonne shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion
AT oksmananna shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion
AT jensenanjatr shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion
AT goldbergdaniele shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion
AT tolianirajh shedeba175mediatesredbloodcellclusteringthatenhancesmalariaparasitegrowthandenablesimmuneevasion