A Simple Mycobacterial Monomycolated Glycerol Lipid Has Potent Immunostimulatory Activity
A Simple Mycobacterial Monomycolated Glycerol Lipid Has Potent Immunostimulatory Activity
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DOI：
10.4049/jimmunol.182.1.424
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Andersen, Peter
中科院分区：
文献类型：
--
作者：
Andersen, Claire S.;Agger, Else Marie;Andersen, Peter
长期以来，人们一直认为牛分枝杆菌卡介苗和弗氏完全佐剂的强免疫刺激活性是由于特定的分枝杆菌细胞包膜成分，如脂质和多糖。与之相关的分枝杆菌脂质包括所谓的脊髓因子或海藻糖二聚酸盐，但有关与人类apc相互作用的刺激成分的精确分子性质的信息有限。在这方面，大多数旨在鉴定和表征个体免疫刺激分枝杆菌脂质的研究都是在小鼠系统中使用骨髓来源的树突状细胞进行的。在这项研究中，它被证明，有效的免疫刺激活性在于芽孢杆菌卡尔梅特- guerin非极性脂类。这种活性可以缩小到一种非常简单的单酵母菌甘油（MMG），通过激活标记物的增强表达和促炎细胞因子的释放来评估其刺激人类树突状细胞的能力。发现基于32个碳（C-32）的MMG的合成类似物具有相当水平的免疫刺激活性。用结核候选疫苗Ag85B-ESAT-6在MMG或合成类似物中免疫小鼠，使用阳离子脂质体作为递送载体，发现可引起显著的Th1应答，其特征是ifn - γ水平显著升高。总之，这一进展开辟了生产一类新型化学定义的脂质佐剂的可能性，以增强针对包括结核病在内的传染性病原体的新疫苗制剂的活性。免疫学杂志，2009,18(2):424-432。
It is a long held belief that the strong immunostimulatory activity of the Mycobacterium bovis bacillus Calmette-Guerin vaccine and Freund's complete adjuvant is due to specific mycobacterial cell envelope components, such as lipids and polysaccharides. Implicated mycobacterial lipids include, among others, the so-called cord factor or trehalose dimycolate, but limited information is available regarding the precise molecular nature of the stimulatory components responsible for the interaction with human APCs. In this regard, the majority of research aimed at identifying and characterizing individual immunostimulatory mycobacterial lipids has been performed in the murine system using bone marrow-derived dendritic cells. In this study, it is documented that potent immunostimulatory activity lies within the bacillus Calmette-Guerin nonpolar lipid class. This activity can be narrowed down to a remarkably simple monomycolyl glycerol (MMG) with the ability to stimulate human dendritic cells as assessed by enhanced expression of activation markers and the release of proinflammatory cytokines. A synthetic analog of MMG based on 32 carbons (C-32) was found to exhibit comparable levels of immunostimulatory activities. Immunization of mice with the tuberculosis vaccine candidate, Ag85B-ESAT-6, in MMG or the synthetic analog using cationic liposomes as the delivery vehicle was found to give rise to a prominent Th1 response characterized by significant levels of IFN-gamma. Together, this development opens up the possibility of producing a novel class of chemically defined lipid adjuvants to enhance the activity of new vaccine formulations, directed against infectious agents including tuberculosis. The Journal of Immunology, 2009, 182: 424-432.