Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion
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- Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion
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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.
Original language | English |
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Article number | e43224 |
Journal | eLife |
Volume | 7 |
Number of pages | 18 |
ISSN | 2050-084X |
DOIs | |
Publication status | Published - 2018 |
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