Lourenço Elaine V, Bernardes Emerson S, Silva Neide M, Mineo José R, Panunto-Castelo Ademilson, Roque-Barreira Maria-Cristina
Laboratório de Imunoquímica e Glicobiologia, Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. dos Bandeirantes, 3900, Ribeirão Preto-SP, CEP 14.049-900, Brazil.
Microbes Infect. 2006 Apr;8(5):1244-51. doi: 10.1016/j.micinf.2005.11.013. Epub 2006 Jan 19.
Host cell invasion by Toxoplasma gondii is tightly coupled to the apical release of micronemal proteins (MIC). In this work, we evaluated the protective effect encountered in C57BL/6 mice immunized with MIC1 and MIC4 purified from soluble tachyzoite antigens by affinity to immobilized lactose. The immunized mice presented high serum levels of IgG1 and IgG2b specific antibodies. MIC1/4-stimulated spleen cells from immunized mice produced IL-2, IL-12, IFN-gamma, IL-10, but not IL-4, suggesting the induction of a polarized Th1 type immune response. When orally challenged with 40 cysts of the ME49 strain, the immunized mice had 68% fewer brain cysts than the control mice. Immunization was associated with 80% survival of the mice challenged with 80 cysts, contrasting with 100% mortality of the non-immunized mice in the acute phase. In this phase, there was much lower parasitism in the lungs and small intestine of the immunized mice, and they did not exhibit the early-stage signs of intestinal necrosis, which was clearly detected in the control mice. Our data demonstrate that MIC1 and MIC4 triggered a protective response against toxoplasmosis, and that these antigens are targets for the further development of a vaccine.
刚地弓形虫对宿主细胞的侵袭与微线体蛋白(MIC)从顶端释放紧密相关。在本研究中,我们评估了用通过固定化乳糖亲和从可溶性速殖子抗原中纯化得到的MIC1和MIC4免疫C57BL/6小鼠所产生的保护作用。免疫小鼠呈现出高血清水平的IgG1和IgG2b特异性抗体。来自免疫小鼠的MIC1/4刺激的脾细胞产生IL-2、IL-12、IFN-γ、IL-10,但不产生IL-4,提示诱导了极化的Th1型免疫反应。当用40个ME49株包囊经口攻击时,免疫小鼠的脑包囊比对照小鼠少68%。免疫与用80个包囊攻击时80%的小鼠存活相关,与之形成对比的是,未免疫小鼠在急性期的死亡率为100%。在此阶段,免疫小鼠的肺和小肠中的寄生现象要低得多,并且它们没有表现出对照小鼠中明显检测到的肠道坏死早期迹象。我们的数据表明,MIC1和MIC4引发了针对弓形虫病的保护反应,并且这些抗原是进一步开发疫苗的靶点。