Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion
- Washington University School of Medicine, United States
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
- University of Copenhagen, Denmark
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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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.
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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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
