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. / Paing, May M; Salinas, Nichole D; Adams, Yvonne; Oksman, Anna; Jensen, Anja TR; Goldberg, Daniel E; Tolia, Niraj H.
In: eLife, Vol. 7, e43224, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2018
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.
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.
U2 - 10.7554/eLife.43224
DO - 10.7554/eLife.43224
M3 - Journal article
C2 - 30556808
VL - 7
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e43224
ER -
ID: 210836012