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Elife. 2018 Dec 17;7. pii: e43224. doi: 10.7554/eLife.43224.

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

Author information

1
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United States.
2
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
3
Centre for Medical Parasitology at Department of Immunology and Microbiology (ISIM), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
4
Department of Medicine, Washington University School of Medicine, St. Louis, United States.
#
Contributed equally

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.

KEYWORDS:

P. falciparum; antibody; evasion; growth; infectious disease; malaria; microbiology

PMID:
30556808
PMCID:
PMC6305201
DOI:
10.7554/eLife.43224
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

MP, NS, YA, AO, AJ, DG, NT No competing interests declared

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