title: α2-3 Sialic acid glycoconjugate loss and its effect on infection with Toxoplasma parasites.
abstract: Recognition of sialylated glycoconjugates is important for host cell invasion by Apicomplexan parasites. Toxoplasma gondii parasites penetrate host cells via interactions between their microneme proteins and sialylated glycoconjugates on the surface of host cells. However, the role played by sialic acids during infection with T. gondii is not well understood. Here, we focused on the role of α2-3 sialic acid linkages as they appear to be widely expressed in vertebrates. Removal of α2-3 sialic acid linkages on macrophages by neuraminidase treatment did not influence the rate of infection or growth of T. gondii, nor did it affect phagocytosis in vitro. Sialyltransferase ST3Gal-I deficient mice (ST3Gal-I(-/-) mice) lost α2-3 sialic acid linkages in macrophages and spleen cells. The numbers of T. gondii-infected CD11b(+) cells in peritoneal cavities of the infected ST3Gal-I(-/-) mice were relatively lower than those of the infected wild type animals. In addition, CD8(+) T cell populations and numbers in the spleens and peritoneal cavities of the ST3Gal-I(-/-) mice were significantly lower than those in the wild type animals before and after the T. gondii infection. ST3Gal-I(-/-) mice had severe liver damage and reduced survival rates following peritoneal infection with T. gondii. Furthermore, adoptive transfer of immune CD8(+) cells from wild type mice to ST3Gal-I(-/-) mice increased their survival during infection with T. gondii. Our data show that parasite invasion via α2-3 sialic acid linkages might not contribute on host survival and indicate the impact that loss of α2-3 sialic acid linkages has on CD8(+) T cell populations, which are necessary for effective immune responses against infection with T. gondii.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. Electronic address: nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Ogiso
authors.forename: Kyohko
authors.initials: K
authors.lastname: Kameyama
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Xuenan
authors.initials: X
authors.lastname: Xuan
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D006001:Glycoconjugates / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000469:parasitology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism*; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D014122:Toxoplasma / Q000276:immunology / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014709:Vero Cells
chemical_list: D006001:Glycoconjugates; D012794:Sialic Acids; D012799:Sialyltransferases
keywords: CD8; ST3Gal-I; Sialic acid; Toxoplasma gondii; α2-3 Sialic acid linkage