小柯机器人

Akkermansia muciniphila磷脂可诱导稳态免疫反应
2022-07-31 00:41

美国哈佛大学医学院Jon Clardy和Ramnik J. Xavier小组合作取得一项新突破。他们发现Akkermansia muciniphila磷脂诱导稳态免疫反应。相关论文于2022年7月27日发表在《自然》杂志上。

研究人员从A. muciniphila细胞膜中鉴定出一种脂质,该脂质在细胞测定中可代表A. muciniphila的免疫调节活性。分离得到的免疫原是一种具有两条支链(a15:0-i15:0 PE)的二酰基磷脂酰乙醇胺,并通过光谱分析和化学合成进行了表征。a15:0-i15:0 PE的免疫原活性具有高度的结构特异性,其免疫信号传导需要toll样受体TLR2-TLR1的异二聚体。

该磷脂的某些活性特征值得注意:它的效力明显低于已知天然和合成的TLR2激动剂;它优先诱导一些炎性细胞因子而非其他;并且在低剂量(EC50的1%)时,它会重置免疫信号的激活阈值和反应。鉴定该分子和等效的合成类似物、其非经典TLR2-TLR1信号通路、其免疫调节选择性和低剂量免疫调节作用,为A. muciniphila在健康和疾病个体中的免疫基调能力及其不同作用模型提供了分子机制。

研究人员表示,很多研究证明了人类肠道细菌与宿主生理学之间的关联,但确定这些关联背后的分子机制仍具有挑战性。Akkermansia muciniphila与宿主代谢、癌症免疫治疗中检查点阻断和稳态免疫的正向结果密切相关。

附:英文原文

Title: Akkermansia muciniphila phospholipid induces homeostatic immune responses

Author: Bae, Munhyung, Cassilly, Chelsi D., Liu, Xiaoxi, Park, Sung-Moo, Tusi, Betsabeh Khoramian, Chen, Xiangjun, Kwon, Jaeyoung, Filipk, Pavel, Bolze, Andrew S., Liu, Zehua, Vlamakis, Hera, Graham, Daniel B., Buhrlage, Sara J., Xavier, Ramnik J., Clardy, Jon

Issue&Volume: 2022-07-27

Abstract: Multiple studies have established associations between human gut bacteria and host physiology, but determining the molecular mechanisms underlying these associations has been challenging1,2,3. Akkermansia muciniphila has been robustly associated with positive systemic effects on host metabolism, favourable outcomes to checkpoint blockade in cancer immunotherapy and homeostatic immunity4,5,6,7. Here we report the identification of a lipid from A. muciniphila’s cell membrane that recapitulates the immunomodulatory activity of A. muciniphila in cell-based assays8. The isolated immunogen, a diacyl phosphatidylethanolamine with two branched chains (a15:0-i15:0 PE), was characterized through both spectroscopic analysis and chemical synthesis. The immunogenic activity of a15:0-i15:0 PE has a highly restricted structure–activity relationship, and its immune signalling requires an unexpected toll-like receptor TLR2–TLR1 heterodimer9,10. Certain features of the phospholipid’s activity are worth noting: it is significantly less potent than known natural and synthetic TLR2 agonists; it preferentially induces some inflammatory cytokines but not others; and, at low doses (1% of EC50) it resets activation thresholds and responses for immune signalling. Identifying both the molecule and an equipotent synthetic analogue, its non-canonical TLR2–TLR1 signalling pathway, its immunomodulatory selectivity and its low-dose immunoregulatory effects provide a molecular mechanism for a model of A. muciniphila’s ability to set immunological tone and its varied roles in health and disease.

DOI: 10.1038/s41586-022-04985-7

Source: https://www.nature.com/articles/s41586-022-04985-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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