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人类适应性免疫力挽救了天生的免疫力错误

Laura Israel¹, Ying Wang², Katarzyna Bulek³

¹Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, 75015 Paris, France; Paris Descartes University, Imagine Institute, 75015 Paris, France.

|February 25, 2017

概括

在单一性疾病中,不完全的透性是由获得的抗体解释的. 遗传的TIRAP缺陷只会导致葡萄球菌疾病,如果还缺少LTA特异性抗体.

科学领域:

免疫学
遗传学
传染性疾病

背景情况:

单一性疾病往往表现出不完全的透性,这种现象在分子层面上尚不完全理解.
托尔类受体 (TLR) 介导的免疫对于对抗像葡萄球菌这样的细菌病原体至关重要.
对于TLR信号传递,TIRAP (Toll-interleukin 1受体域含有的适配蛋白) 是必不可少的.

研究的目的:

调查自体递归TIRAP缺乏的不完全透的分子基础.
了解TIRAP和获得的抗体对葡萄球菌感染敏感性的作用.

主要方法:

研究了8名与TIRAP自体衰退缺乏症相关的个体.
在患者的纤维细胞和白细胞中评估了对Toll类受体激活剂的细胞反应.
研究了抗脂质醇酸 (LTA) 单克隆抗体 (mAb) 对患者和小鼠模型免疫反应的影响.

主要成果:

所有TIRAP缺乏的个体对TLR1/ 2,TLR2/ 6和TLR4激动剂的反应有损.
只有缺乏LTA特异性抗体 (Abs) 的试验对象对TLR2/ 6激动剂LTA完全没有反应.
在TIRAP缺乏的个体和小鼠中获得的抗LTAAbs恢复了TLR2依赖性免疫力,这种效应依赖于TIRAP,但不是TLR2或MyD88.

结论:

获得的抗LTA Abs可以在TIRAP遗传性缺陷的个体中恢复TLR2依赖的免疫力,这解释了不完全的透性.
结合的TIRAP和抗LTA Ab缺陷导致了试验对象的严重葡萄球菌病.
这项研究强调了遗传性免疫缺陷与获得性免疫在疾病发病过程中的相互作用.

关键词:

一个LTA 国际货币基金组织抗LTA抗体不完全的临床透率利波泰可酸一次性免疫缺陷黄金葡萄球菌类似收费的接收器

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