一个原生动物的林样蛋白激活树突细胞的TLR11激活
Felix Yarovinsky1, Dekai Zhang, John F Andersen
1Immunobiology Section, Laboratory of Parasitic Diseases; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. fyarovinsky@niaid.nih.gov
Science (New York, N.Y.)
|April 30, 2005
概括
毒素原生菌的蛋白质激活了树突细胞 (DCs) 通过托尔类受体11 (TLR11),这是对原生虫寄生虫的先天免疫的关键途径. 这一发现突出了TLR11的发现.
科学领域:
- 免疫学 免疫学 免疫学
- 寄生虫学的寄生虫学
- 细胞生物学 细胞生物学
背景情况:
- 哺乳动物的Toll-like受体 (TLRs) 对于先天免疫至关重要,主要用于细菌和病毒病原体的识别.
- 在对真核微生物,如原生虫寄生虫的反应中TLRs的作用仍然不太清楚.
- 树突细胞 (DCs) 是关键的免疫细胞,参与病原体的感知和启动适应性免疫反应.
研究的目的:
- 识别原生虫寄生虫Toxoplasma gondii的分子,这些分子可以激活树突细胞中的先天免疫反应.
- 为了研究参与识别T. gondii组件的特定Toll样受体 (TLR).
- 为了确定这种识别途径对宿主防御寄生虫感染的体内相关性.
主要方法:
- 从Toxoplasma gondii中分离和表征一种类似型分子.
- 在实验室中用已识别的分子刺激小鼠树突细胞 (DCs).
- 评估细胞因子的产生 (例如IL-12) 和TLR依赖的信号通路 (例如MyD88).
- 使用淘汰赛小鼠进行体内研究,以确定TLR11对寄生虫耐药性的必要性.
主要成果:
- 来自T. gondii的一种类似蛋白质的分子被确定为小鼠DCs的强有力的激活剂.
- 这种激活取决于骨髓样分化因子88 (MyD88) 并由托尔类受体11 (TLR11) 特别介导.
- 鉴定出T. gondii profilin是TLR11的第一个化学定义的连接体.
- 发现TLR11在体内对寄生虫诱导的IL-12产生和有效抵抗T. gondii感染至关重要.
结论:
- 托克索普拉斯马淋巴状蛋白作为TLR11的连接体,在树突细胞中启动MyD88依赖的IL-12反应.
- TLR11在原生动物寄生虫的天生的免疫识别中发挥着关键作用.
- 这项研究确立了TLR11与宿主防御T. gondii之间的直接联系,突出了它在识别真核病原体中的重要性.
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