Erythrocyte invasion by Babesia parasites: current advances in the elucidation of the molecular interactions between the protozoan ligands and host receptors in the invasion stage.

During an asexual growth cycle of Babesia parasites in a natural host, the extracellular merozoites invade (i.e., attach to, penetrate, and internalize) the host erythrocytes (RBC) via multiple adhesive interactions of several protozoan ligands with the target receptors on the host cell surface. After internalizing the host RBC, they asexually multiply, egress from the RBC by rupturing the host cells, and then invade the new RBC again. In the invasion stage, several surface-coating molecules of merozoites might be involved in the initial attachment to the RBC, while proteins secreted from apical organelles (rhoptry, microneme, and spherical body) are proposed to play roles mainly in erythrocyte penetration or internalization. On the other hand, several components located on the surface of the RBC, such as sialic acid residues, protease-sensitive proteins, or sulphated glycosaminoglycans, are identified or suspected as the host receptors of erythrocyte invasion by Babesia parasites. The detailed molecular interactions between Babesia merozoites and the host RBC are incompletely understood. In this review, these identified or suspected molecules (protozoan ligands/erythrocyte receptors) are described by especially focusing on Babesia bovis.