A Novel Exopolysaccharide from the Biofilm of Thermus aquaticus YT-1 Induces the Immune Response through Toll-like Receptor 2
A Novel Exopolysaccharide from the Biofilm of Thermus aquaticus YT-1 Induces the Immune Response through Toll-like Receptor 2
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DOI：
10.1074/jbc.m110.200113
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发表时间：
2011-05-20
影响因子：
4.8
通讯作者：
Wu, Shih-Hsiung
中科院分区：
文献类型：
--
作者：
Lin, Miao-Hsia;Yang, Yu-Liang;Wu, Shih-Hsiung
已知细菌多糖可诱导巨噬细胞的免疫反应。本文从水热菌（Thermus aquaticus）的生物膜中分离出一种新的胞外多糖，并对其结构和免疫调节作用进行了评价。该多糖TA-1的大小通过排粒径色谱法推断为500 kDa。GC-MS，高效阴离子交换色谱-脉冲安培检测，电喷雾电离-MS/MS和NMR揭示了TA-1的新结构。该多糖由半乳糖呋喃糖、半乳糖吡喃糖和n -乙酰半乳糖胺（1:1:2）的四糖重复单元组成，不含酸性糖。TA-1刺激巨噬细胞产生细胞因子tnf - α和IL-6。toll样受体的筛选和抗体阻断实验表明，TA-1免疫活性的天然受体是TLR2。在野生型小鼠腹膜巨噬细胞中，TA-1诱导IL-6产生证实了TA-1被TLR2识别，而TLR2（-/-）小鼠腹膜巨噬细胞中则没有。TA-1作为TLR2激动剂，可以作为佐剂，促进细胞因子的释放，提高免疫应答。此外，TA-1诱导的细胞因子释放依赖于MyD88/TIRAP。
Bacterial polysaccharides are known to induce the immune response in macrophages. Here we isolated a novel extracellular polysaccharide from the biofilm of Thermus aquaticus YT-1 and evaluated its structure and immunomodulatory effects. The size of this polysaccharide, TA-1, was deduced by size-exclusion chromatography as 500 kDa. GC-MS, high performance anion-exchange chromatography with pulsed amperometric detection, electrospray ionization-MS/MS, and NMR revealed the novel structure of TA-1. The polysaccharide is composed of tetrasaccharide-repeating units of galactofuranose, galactopyranose, and N-acetylgalactosamine (1: 1: 2) and lacked acidic sugars. TA-1 stimulated macrophage cells to produce the cytokines TNF-alpha and IL-6. Screening of Toll-like receptors and antibody-blocking experiments indicated that the natural receptor of TA-1 in its immunoactivity is TLR2. Recognition of TA-1 by TLR2 was confirmed by TA-1 induction of IL-6 production in peritoneal macrophages from wild-type mice but not from TLR2 (-/-) mice. TA-1, as a TLR2 agonist, could possibly be used as an adjuvant and could enhance cytokine release, which increases the immune response. Furthermore, TA-1 induced cytokine release is dependent on MyD88/TIRAP.