National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
Exp Parasitol. 2013 Nov;135(3):479-85. doi: 10.1016/j.exppara.2013.08.009. Epub 2013 Aug 27.
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.
唾液酸糖缀合物的识别对于顶复门寄生虫感染宿主细胞至关重要。刚地弓形虫寄生虫通过其微线蛋白与宿主细胞表面的唾液酸化糖缀合物之间的相互作用穿透宿主细胞。然而，在刚地弓形虫感染过程中，唾液酸的作用尚未得到很好的理解。在这里，我们专注于α2-3 唾液酸连接的作用，因为它们似乎在脊椎动物中广泛表达。用神经氨酸酶处理巨噬细胞以去除α2-3 唾液酸连接不会影响刚地弓形虫的感染率或生长速度，也不会影响体外吞噬作用。唾液酸转移酶 ST3Gal-I 缺陷型小鼠（ST3Gal-I(-/-) 小鼠）在巨噬细胞和脾细胞中失去了α2-3 唾液酸连接。感染 ST3Gal-I(-/-) 小鼠腹腔内感染的 CD11b(+) 细胞数量相对低于感染野生型动物的数量。此外，在感染前后，ST3Gal-I(-/-) 小鼠的脾和腹腔中的 CD8(+) T 细胞群体和数量均明显低于野生型动物。ST3Gal-I(-/-) 小鼠在经腹膜感染刚地弓形虫后出现严重的肝损伤和存活率降低。此外，从野生型小鼠向 ST3Gal-I(-/-) 小鼠过继转移免疫 CD8(+) 细胞可提高其在感染刚地弓形虫时的存活率。我们的数据表明，寄生虫通过α2-3 唾液酸连接的入侵可能不会影响宿主的存活，并表明丧失α2-3 唾液酸连接对 CD8(+) T 细胞群体的影响，这对于针对刚地弓形虫感染的有效免疫反应是必要的。
