Glycophorin A-knockout mice, which lost sialoglycoproteins from the red blood cell membrane, are resistant to lethal infection of Babesia rodhaini

Recent in vitro-based studies using several Babesia spp. have suggested that sialic acids and/or sialoglycoproteins on host red blood cells (RBCs) play an important role in their invasion of RBCs. In the present study, we analyzed the RBC characteristics of glycophorin A (GPA)-knockout mice and studied their in vivo susceptibility to lethal infection of Babesia rodhaini for the first time. In immunoblot and lectin blot analyses, glycoproteins containing O-linked oligosaccharides terminated with α2-3-linked sialic acids disappeared from the RBCs of GPA homozygous (−/−) mice. Flow cytometric analysis showed a remarkable reduction of Maackia amurensis lectin II binding to the surface of GPA−/− RBCs relative to control RBCs, indicating an appreciable loss of α2-3-linked sialic acids on the RBC surface of GPA−/− mice. Importantly, while B. rodhaini caused lethal infection in wild-type mice, the infected GPA−/− mice showed inhibition of parasite growth and eventually survived. These results indicate that RBC sialoglycoproteins lost in GPA−/− mice are involved in the in vivo growth of B. rodhaini, probably functioning as essential molecule(s) for the parasite invasion of host RBCs in the blood circulation.