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

TY - JOUR

T1 - Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion

AU - Paing, May M

AU - Salinas, Nichole D

AU - Adams, Yvonne

AU - Oksman, Anna

AU - Jensen, Anja TR

AU - Goldberg, Daniel E

AU - Tolia, Niraj H

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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. DOI: https://doi.org/10.7554/eLife.43224.001.

AB - 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. DOI: https://doi.org/10.7554/eLife.43224.001.

U2 - 10.7554/eLife.43224

DO - 10.7554/eLife.43224

M3 - Journal article

C2 - 30556808

SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - e43224

ER -