阿克尔曼西亚菌脂诱导恒常性免疫反应
Munhyung Bae1,2, Chelsi D Cassilly1, Xiaoxi Liu1,3
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA, USA.
Nature
|July 27, 2022
概括
研究人员发现肠道细菌Akkermansia muciniphila中有一种特定的脂质, 这种分子通过独特的收费类受体 (TLR2-TLR1) 途径发出信号,为肠道微生物提供了洞察力
科学领域:
- 微生物学
- 免疫学
- 生物化学
背景情况:
- 人类肠道微生物组影响宿主生理,但分子机制尚不清楚.
- 艾克曼西亚菌与改善新陈代谢,癌症免疫疗法和免疫平衡有关.
- 了解A. muciniphila的功能需要识别其活性分子组成部分.
研究的目的:
- 确定负责A. muciniphila免疫调节活动的特定分子.
- 阐明这种已识别的分子的分子机制和信号通路.
- 探索该分子的结构-活性关系和剂量依赖性影响.
主要方法:
- 从A. muciniphila细胞膜中分离和表征脂质.
- 鉴定脂质的光谱分析和化学合成.
- 基于细胞的测试以评估免疫调节活性和信号通路激活 (TLR2-TLR1).
主要成果:
- 一种具有分支链的二甲基酸乙醇胺 (a15: 0- i15: 0 PE) 被确定为免疫原.
- a15:0-i15:0 PE信号通过一个意想不到的收费类受体TLR2-TLR1异构体.
- 该分子具有选择性细胞因子诱导和低剂量免疫调节作用,与其他TLR2激动剂不同.
结论:
- 来自A. muciniphila的特定脂质a15:0-i15:0PE解释了它的免疫调节特性.
- 非正规的TLR2-TLR1通路对于这种脂质的免疫信号传递至关重要.
- 这一发现为A. muciniphila在调节宿主免疫力和健康方面的作用提供了分子基础.
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