1. Microbiology and Infectious Disease

Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion

  1. May M Paing
  2. Nichole D Salinas
  3. Yvonne Adams
  4. Anna Oksman
  5. Anja TR Jensen
  6. Daniel E Goldberg
  7. Niraj H Tolia  Is a corresponding author
  1. Washington University School of Medicine, United States
  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
  3. University of Copenhagen, Denmark
https://doi.org/10.7554/eLife.43224
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Cite this article
  1. May M Paing
  2. Nichole D Salinas
  3. Yvonne Adams
  4. Anna Oksman
  5. Anja TR Jensen
  6. Daniel E Goldberg
  7. Niraj H Tolia
(2018)
Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion
eLife 7:e43224.
https://doi.org/10.7554/eLife.43224
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Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. May M Paing

    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Nichole D Salinas

    Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Yvonne Adams

    Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.

  4. Anna Oksman

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Anja TR Jensen

    Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4004-7554

  6. Daniel E Goldberg

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3529-8399

  7. Niraj H Tolia

    Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
    For correspondence
    niraj.tolia@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2689-1337

Funding

National Institutes of Health

  • May M Paing
  • Nichole D Salinas
  • Niraj H Tolia

Burroughs Wellcome Fund

  • Niraj H Tolia

National Institute of Allergy and Infectious Diseases

  • Nichole D Salinas
  • Niraj H Tolia

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: October 29, 2018
  2. Accepted: December 14, 2018
  3. Accepted Manuscript published: December 17, 2018 (version 1)
  4. Version of Record published: December 24, 2018 (version 2)

Copyright

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.

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  1. May M Paing
  2. Nichole D Salinas
  3. Yvonne Adams
  4. Anna Oksman
  5. Anja TR Jensen
  6. Daniel E Goldberg
  7. Niraj H Tolia
(2018)
Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion
eLife 7:e43224.
https://doi.org/10.7554/eLife.43224

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