• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

TREM2 是分枝杆菌非糖基化的类脂阿拉伯甘露糖的受体，它限制了抗分枝杆菌的巨噬细胞的激活。

TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.

机构信息

Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Research and Development Department, Japan BCG Laboratory, Tokyo, Japan.

出版信息

Nat Commun. 2021 Apr 16;12(1):2299. doi: 10.1038/s41467-021-22620-3.

DOI:10.1038/s41467-021-22620-3
PMID:33863908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8052348/
Abstract

Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages respond to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages respond to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhances Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.

摘要

分枝杆菌细胞壁糖脂通过 FcRγ 相关 C 型凝集素受体（包括 Mincle 和 caspase 募集结构域家族成员 9（CARD9））引发抗分枝杆菌免疫反应。此外，分枝杆菌还具有与毒力和潜伏相关的免疫逃避细胞壁脂质；然而，其作用机制尚不清楚。在这里，我们表明，髓样细胞表达的 DAP12 相关触发受体 2（TREM2）识别分枝杆菌细胞壁含有酰基的分枝菌酸（MA）的脂质，并提出了一种分枝杆菌通过 TREM2 控制宿主免疫的机制。巨噬细胞以依赖于 Mincle/FcRγ/CARD9 的方式对糖基化 MA 脂质作出反应，以产生炎症细胞因子并招募诱导型一氧化氮合酶（iNOS）阳性的杀分枝杆菌巨噬细胞。相反，巨噬细胞以依赖于 TREM2/DAP12 但不依赖于 CARD9 的方式对非糖基化的 MA 作出反应，以招募 iNOS 阴性的分枝杆菌允许的巨噬细胞。此外，TREM2 缺失增强了体外 Mincle 诱导的巨噬细胞活化和体内炎症，并加速了分枝杆菌感染的消除，这表明 TREM2-DAP12 信号传导拮抗了 Mincle-FcRγ-CARD9 介导的抗分枝杆菌免疫。因此，分枝杆菌利用 TREM2 进行免疫逃避。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/6cafadf1ad78/41467_2021_22620_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/8648a5d28729/41467_2021_22620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/883093c04a7f/41467_2021_22620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/41abc3455666/41467_2021_22620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/49e254ffa022/41467_2021_22620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/1c059d0c199d/41467_2021_22620_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/198d53f03398/41467_2021_22620_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/6cafadf1ad78/41467_2021_22620_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/8648a5d28729/41467_2021_22620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/883093c04a7f/41467_2021_22620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/41abc3455666/41467_2021_22620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/49e254ffa022/41467_2021_22620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/1c059d0c199d/41467_2021_22620_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/198d53f03398/41467_2021_22620_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de4/8052348/6cafadf1ad78/41467_2021_22620_Fig7_HTML.jpg

相似文献

1
TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.TREM2 是分枝杆菌非糖基化的类脂阿拉伯甘露糖的受体，它限制了抗分枝杆菌的巨噬细胞的激活。
Nat Commun. 2021 Apr 16;12(1):2299. doi: 10.1038/s41467-021-22620-3.
2
Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by Mycobacterial Cord Factor and the Novel Adjuvant TDB.甘露糖受体C型凝集素-脾酪氨酸激酶信号传导对分枝杆菌索状因子和新型佐剂TDB激活原代人抗原呈递细胞的作用
J Immunol. 2015 Sep 1;195(5):2417-28. doi: 10.4049/jimmunol.1500102. Epub 2015 Jul 22.
3
TREM2 Promotes Immune Evasion by Mycobacterium tuberculosis in Human Macrophages.TREM2 促进结核分枝杆菌在人巨噬细胞中的免疫逃逸。
mBio. 2022 Aug 30;13(4):e0145622. doi: 10.1128/mbio.01456-22. Epub 2022 Aug 4.
4
C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation.C型凝集素受体dectin-3通过CARD9/Bcl10/MALT1依赖的核因子(NF)-κB激活介导海藻糖6,6'-二霉菌酸酯(TDM)诱导的Mincle表达。
J Biol Chem. 2014 Oct 24;289(43):30052-62. doi: 10.1074/jbc.M114.588574. Epub 2014 Sep 8.
5
Evidence for TLR4 and FcRγ-CARD9 activation by cholera toxin B subunit and its direct bindings to TREM2 and LMIR5 receptors.霍乱毒素B亚基激活TLR4和FcRγ-CARD9的证据及其与TREM2和LMIR5受体的直接结合。
Mol Immunol. 2015 Aug;66(2):463-71. doi: 10.1016/j.molimm.2015.05.008. Epub 2015 May 26.
6
Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids.Toll样受体2和巨噬细胞C型凝集素协同感知棒状杆菌细胞壁糖脂
Infect Immun. 2017 Jun 20;85(7). doi: 10.1128/IAI.00075-17. Print 2017 Jul.
7
Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge.分枝杆菌受体Clec4d（CLECSF8，MCL）与Mincle共同调节，在微生物攻击后小鼠髓样细胞上上调。
Eur J Immunol. 2016 Feb;46(2):381-9. doi: 10.1002/eji.201545858. Epub 2015 Dec 8.
8
Triggering receptor expressed on myeloid cells 2 (TREM2) dependent microglial activation promotes cisplatin-induced peripheral neuropathy in mice.髓样细胞表达的触发受体 2（TREM2）依赖性小胶质细胞激活促进了小鼠顺铂诱导的周围神经病。
Brain Behav Immun. 2018 Feb;68:132-145. doi: 10.1016/j.bbi.2017.10.011. Epub 2017 Oct 16.
9
Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.前沿：Mincle 对于分枝杆菌 Cord 因子及其合成类似物海藻糖二硬脂酸酯的识别和佐剂活性至关重要。
J Immunol. 2010 Mar 15;184(6):2756-60. doi: 10.4049/jimmunol.0904013. Epub 2010 Feb 17.
10
Mycobacterial mycolic acids trigger inhibitory receptor Clec12A to suppress host immune responses.分枝杆菌的菌壁酸触发抑制性受体 Clec12A 抑制宿主免疫反应。
Tuberculosis (Edinb). 2023 Jan;138:102294. doi: 10.1016/j.tube.2022.102294. Epub 2022 Dec 13.

引用本文的文献

1
Single-cell transcriptomic profiling reveals a novel signature of necrotizing granulomatous lesions in the lungs of -infected C3HeB/FeJ mice.单细胞转录组分析揭示了感染的C3HeB/FeJ小鼠肺部坏死性肉芽肿病变的一种新特征。
Front Immunol. 2025 Aug 6;16:1624072. doi: 10.3389/fimmu.2025.1624072. eCollection 2025.
2
Loss of disrupts plasma membrane domains and promotes free mycolic acid accumulation in mycobacteria.[某种物质]的缺失会破坏质膜结构域，并促进分枝杆菌中游离霉菌酸的积累。 （注：原文中“Loss of ”这里缺失了具体物质，所以翻译时加了“[某种物质]”）
bioRxiv. 2025 Aug 5:2025.08.05.668640. doi: 10.1101/2025.08.05.668640.
3
Stopping Tuberculosis at the Gate: The Role of Adhesins in Infection and Intervention.

本文引用的文献

1
Adjuvant activity of -derived mycolic acids.源自结核分枝杆菌的分枝菌酸的佐剂活性。 （注：这里的“-derived”推测可能是“mycobacterium-derived”之类表示源自某种杆菌的，原英文表述不太完整准确）
Heliyon. 2020 May 27;6(5):e04064. doi: 10.1016/j.heliyon.2020.e04064. eCollection 2020 May.
2
The mycobacterial cell envelope - a moving target.分枝杆菌的细胞包膜——一个移动的目标。
Nat Rev Microbiol. 2020 Jan;18(1):47-59. doi: 10.1038/s41579-019-0273-7. Epub 2019 Nov 14.
3
Tuberculosis vaccine candidates based on mycobacterial cell envelope components.基于分枝杆菌细胞包膜成分的结核疫苗候选物。
在源头遏制结核病：黏附素在感染与干预中的作用
Vaccines (Basel). 2025 Jun 24;13(7):676. doi: 10.3390/vaccines13070676.
4
Development and Validation of Early Alert Model for Diabetes Mellitus-Tuberculosis Comorbidity.糖尿病合并结核病早期预警模型的开发与验证
Microorganisms. 2025 Apr 16;13(4):919. doi: 10.3390/microorganisms13040919.
5
A Photoactivatable Free Mycolic Acid Probe to Investigate Mycobacteria-Host Interactions.一种用于研究分枝杆菌与宿主相互作用的光可激活游离分枝菌酸探针。
ACS Infect Dis. 2025 May 9;11(5):1233-1245. doi: 10.1021/acsinfecdis.5c00068. Epub 2025 Apr 14.
6
TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity.触发受体表达于髓系细胞2（TREM2）通过控制肺泡巨噬细胞的存活和促纤维化活性来促进肺纤维化。
Nat Commun. 2025 Feb 19;16(1):1761. doi: 10.1038/s41467-025-57024-0.
7
Single-cell analysis reveals ESX-1-mediated accumulation of permissive macrophages in infected mouse lungs.单细胞分析揭示了ESX-1介导的允许性巨噬细胞在感染小鼠肺部的积累。
Sci Adv. 2025 Jan 17;11(3):eadq8158. doi: 10.1126/sciadv.adq8158. Epub 2025 Jan 15.
8
Upregulation of TREM2 expression in M2 macrophages promotes chronic infection.TREM2 表达在 M2 巨噬细胞中的上调促进了慢性感染。
Front Immunol. 2024 Oct 21;15:1466520. doi: 10.3389/fimmu.2024.1466520. eCollection 2024.
9
Deletion of Card9 eliminates the detrimental facets of mycobacterial adjuvants.删除Card9可消除分枝杆菌佐剂的有害方面。
Heliyon. 2024 Sep 19;10(19):e38139. doi: 10.1016/j.heliyon.2024.e38139. eCollection 2024 Oct 15.
10
WRN Nuclease-Mediated EcDNA Clearance Enhances Antitumor Therapy in Conjunction with Trehalose Dimycolate/Mesoporous Silica Nanoparticles.WRN 核酸酶介导的 ecDNA 清除联合海藻糖二肉豆蔻酸酯/介孔硅纳米颗粒增强抗肿瘤治疗。
Adv Sci (Weinh). 2024 Oct;11(40):e2407026. doi: 10.1002/advs.202407026. Epub 2024 Aug 29.
Tuberculosis (Edinb). 2019 Mar;115:26-41. doi: 10.1016/j.tube.2019.01.003. Epub 2019 Jan 22.
4
and lipids: Insights into molecular mechanisms from persistence to virulence.以及脂质：从持续性到毒力的分子机制洞察
J Res Med Sci. 2018 Jul 26;23:63. doi: 10.4103/jrms.JRMS_904_17. eCollection 2018.
5
Phenolic Glycolipid Facilitates Mycobacterial Escape from Microbicidal Tissue-Resident Macrophages.酚糖脂促进分枝杆菌逃离具有杀菌作用的组织驻留巨噬细胞。
Immunity. 2017 Sep 19;47(3):552-565.e4. doi: 10.1016/j.immuni.2017.08.003. Epub 2017 Aug 24.
6
"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.《结核分枝杆菌免疫逃逸对保护性免疫的影响：对结核病疫苗设计的启示》——会议报告
Vaccine. 2017 Jun 14;35(27):3433-3440. doi: 10.1016/j.vaccine.2017.04.007. Epub 2017 May 2.
7
Macrophage Polarization Modulates FcγR- and CD13-Mediated Phagocytosis and Reactive Oxygen Species Production, Independently of Receptor Membrane Expression.巨噬细胞极化调节FcγR和CD13介导的吞噬作用及活性氧生成，与受体膜表达无关。
Front Immunol. 2017 Mar 27;8:303. doi: 10.3389/fimmu.2017.00303. eCollection 2017.
8
Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity.细胞内代谢物β-葡糖脑苷脂是一种具有免疫刺激活性的内源性 Mincle 配体。
Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3285-E3294. doi: 10.1073/pnas.1618133114. Epub 2017 Apr 3.
9
Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response.细菌免疫调节剂：结核分枝杆菌脂质及其在宿主免疫反应中的作用。
Rev Soc Bras Med Trop. 2017 Jan-Feb;50(1):9-18. doi: 10.1590/0037-8682-0230-2016.
10
Mycobacterial Dormancy Systems and Host Responses in Tuberculosis.结核病中的分枝杆菌休眠系统与宿主反应
Front Immunol. 2017 Feb 15;8:84. doi: 10.3389/fimmu.2017.00084. eCollection 2017.