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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。

Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.

机构信息

Institute of Clinical Microbiology, Immunology and Hygiene Medical Department, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Clinics of Erlangen, Erlangen, Germany.

出版信息

J Immunol. 2010 Mar 15;184(6):2756-60. doi: 10.4049/jimmunol.0904013. Epub 2010 Feb 17.


DOI:10.4049/jimmunol.0904013
PMID:20164423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3442336/
Abstract

The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRgamma was essential for macrophage activation and Th17 adjuvanticity. The FcRgamma-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRgamma were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guérin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.

摘要

分枝杆菌 cord 因子海藻糖-6,6-二没食子酸酯 (TDM) 和其合成类似物海藻糖-6,6-二油酰基酯 (TDB) 是 Th1/Th17 疫苗接种的有效佐剂,可激活 APC 中的 Syk-Card9 信号通路。在这项研究中,我们进一步研究了 TDM 和 TDB 对先天免疫激活的分子机制。Syk 偶联衔接蛋白 FcRγ 对于巨噬细胞的激活和 Th17 的佐剂活性是必不可少的。FcRγ 相关的 C 型凝集素受体 Mincle 在巨噬细胞中表达,并可被 TDM 和 TDB 上调。重组 Mincle-Fc 融合蛋白特异性结合糖脂。Mincle 的基因缺失消除了 TDM/TDB 诱导的巨噬细胞激活和对结核亚单位疫苗的 T 细胞免疫反应的诱导。缺乏 Mincle 或 FcRγ 的巨噬细胞在对牛分枝杆菌卡介苗的炎症反应中受损。这些结果表明 Mincle 是分枝杆菌 cord 因子的关键受体,控制 TDM 和 TDB 的 Th1/Th17 佐剂活性。

相似文献

[1]
Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.

J Immunol. 2010-2-17

[2]
Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by Mycobacterial Cord Factor and the Novel Adjuvant TDB.

J Immunol. 2015-9-1

[3]
The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling.

PLoS One. 2013-1-7

[4]
Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C/EBPβ and HIF1α.

J Immunol. 2014-8-25

[5]
IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity.

Elife. 2023-2-8

[6]
C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor.

Immunity. 2013-4-18

[7]
Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo.

Innate Immun. 2016-8

[8]
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.

J Exp Med. 2009-1-16

[9]
Mycobacterial Cord Factor Reprograms the Macrophage Response to IFN-γ towards Enhanced Inflammation yet Impaired Antigen Presentation and Expression of GBP1.

J Immunol. 2020-9-15

[10]
The mycobacterial cord factor adjuvant analogue trehalose-6,6'-dibehenate (TDB) activates the Nlrp3 inflammasome.

Immunobiology. 2012-8-7

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本文引用的文献

[1]
Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle.

J Exp Med. 2009-12-14

[2]
Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils.

Immunity. 2009-11-20

[3]
Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection.

J Exp Med. 2009-8-31

[4]
MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis.

PLoS Pathog. 2009-6

[5]
C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia.

Proc Natl Acad Sci U S A. 2009-2-10

[6]
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.

J Exp Med. 2009-1-16

[7]
Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells.

J Immunol. 2009-1-15

[8]
Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements.

PLoS One. 2008-9-8

[9]
Mincle is an ITAM-coupled activating receptor that senses damaged cells.

Nat Immunol. 2008-10

[10]
Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches.

Cell Stem Cell. 2008-7-3

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