Laboratório de Imunologia e Genômica de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270901, Brazil.
Instituto de Investigación, Centro de Investigación en Inmunología e Infectología, Facultad de Medicina Humana, Universidad de San Martin de Porres, Lima 15000, Perú.
ACS Infect Dis. 2020 Jul 10;6(7):1807-1815. doi: 10.1021/acsinfecdis.0c00061. Epub 2020 May 18.
The leading animal model of experimental Chagas disease, the mouse, plays a significant role in studies for vaccine development, diagnosis, and human therapies. Humans, along with Old World primates, alone among mammals, cannot make the terminal carbohydrate linkage of the α-Gal trisaccharide. It has been established that the anti-α-Gal immune response is likely to be a critical factor for protection against () infection in humans. However, the mice customarily employed for the study of infection naturally express the α-Gal epitope and therefore do not produce anti-α-Gal antibodies. Here, we used the C57BL/6 α-1,3-galactosyltransferase knockout (α-GalT-KO) mouse, which does not express the α-Gal epitope as a model for experimental Chagas disease. We found the anti-α-Gal IgG antibody response to an increase in α-GalT-KO mice infected with and strains of , leading to fewer parasite nests, lower parasitemia, and an increase of INF-γ, TNF-α, and IL-12 cytokines in the heart of α-GalT-KO mice compared with α-GalT-WT mice on days 60 and 120 postinfection. We therefore agree that the C57BL/6 α-GalT-KO mouse represents a useful model for initial testing of therapeutic and immunological approaches against different strains of .
实验性恰加斯病的主要动物模型——小鼠,在疫苗开发、诊断和人类疗法的研究中发挥着重要作用。人类与旧世界灵长类动物一样,是唯一在哺乳动物中不能合成α-Gal 三糖末端碳水化合物连接的物种。已经证实,抗α-Gal 免疫反应可能是人类抵御()感染的关键因素。然而,用于()感染研究的常规小鼠天然表达α-Gal 表位,因此不会产生抗α-Gal 抗体。在这里,我们使用 C57BL/6 α-1,3-半乳糖基转移酶敲除(α-GalT-KO)小鼠作为实验性恰加斯病的模型,该模型不表达α-Gal 表位。我们发现,感染()和()株的α-GalT-KO 小鼠的抗α-Gal IgG 抗体反应增加,导致寄生虫巢减少、寄生虫血症降低,并导致 IFN-γ、TNF-α 和 IL-12 细胞因子在感染后 60 天和 120 天的α-GalT-KO 小鼠心脏中增加,与α-GalT-WT 小鼠相比。因此,我们认为 C57BL/6 α-GalT-KO 小鼠是针对不同()株的治疗和免疫方法进行初步测试的有用模型。