A Cardiolipin from Muribaculum intestinale Induces Antigen-Specific Cytokine Responses.

A Cardiolipin from Muribaculum intestinale Induces Antigen-Specific Cytokine Responses.
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DOI:
10.1021/jacs.3c09734
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发表时间:
2023-11-01
影响因子:
15
通讯作者:
Clardy, Jon
Clardy, Jon
中科院分区:
化学1区
文献类型:
--
作者:
Bang, Sunghee;Shin, Yern-Hyerk;Ma, Xiao;Park, Sung-Moo;Graham, Daniel B.;Xavier, Ramnik J.;Clardy, Jon

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对具有免疫调节作用的小鼠肠道微生物组代谢物进行了系统的表型筛选,发现Muribaculum ninteinale是仅有的两个对t细胞群体具有超大影响的成员之一。在这里,我们报告了一种脂质MiCL-1作为负责代谢物的鉴定和表征。MiCL-1是一种18:1-16:0的心磷脂,其近亲存在于哺乳动物和细菌的凹脂质表面。MiCL-1的合成证实了MiCL-1的结构分析和功能特征。它具有高度限制性的结构-活性特征,因为它的链开关模拟物在我们的任何试验中都无法诱导反应。MiCL-1可诱导TNF-α、IL-6和IL-23等促炎细胞因子的产生,但对抗炎细胞因子IL-10无明显影响。与其他最近发现的免疫调节脂质一样,在基于细胞的检测中,MiCL-1需要功能性TLR2和TLR1,而不需要TLR6。
An systematic phenotypic screen of the mouse gut microbiome for metabolites with an immunomodulatory effect identified Muribaculum intestinale as one of only two members with an oversized effect on T-cell populations. Here we report the identification and characterization of a lipid, MiCL-1, as the responsible metabolite. MiCL-1 is an 18:1-16:0 cardiolipin, whose close relatives are found on concave lipid surfaces of both mammals and bacteria. MiCL-1 was synthesized to confirm the structural analysis and functionally characterized in cell-based assays. It has a highly restrictive structure–activity profile, as its chain-switched analog fails to induce responses in any of our assays. MiCL-1 robustly induces the production of pro-inflammatory cytokines like TNF-α, IL-6, and IL-23, but has no detectable effect on the anti-inflammatory cytokine IL-10. As is the case with other recently discovered immunomodulatory lipids, MiCL-1 requires functional TLR2 and TLR1 but not TLR6 in cell-based assays.
重新审视COLEY的毒素:化脓性链球菌的免疫原生脂蛋白。
DOI: 10.1021/jacs.3c07727
发表时间: 2023-10-04
影响因子: 15
作者:
Shin, Yern-Hyerk;Bang, Sunghee;Park, Sung-Moo;Ma, Xiao;Cassilly, Chelsi;Graham, Daniel;Xavier, Ramnik;Clardy, Jon
通讯作者: Clardy, Jon
DOI: 10.1016/j.immuni.2022.08.016
发表时间: 2022-10-11
期刊: IMMUNITY
影响因子: 32.4
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DOI: 10.1021/jo00032a033
发表时间: 1992-03-13
影响因子: 3.6
作者:
HEBERT, N;BECK, A;JUST, G
通讯作者: JUST, G
DOI: 10.1021/jo960895r
发表时间: 1996-09-06
影响因子: 3.6
作者:
Chen, J;Profit, AA;Prestwich, GD
通讯作者: Prestwich, GD
DOI: 10.1038/s41591-019-0495-2
发表时间: 2019-07-01
期刊: NATURE MEDICINE
影响因子: 82.9
作者:
Depommier, Clara;Everard, Amandine;Cani, Patrice D.
通讯作者: Cani, Patrice D.