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一种来自水生栖热菌 YT-1 生物膜的新型胞外多糖通过 Toll 样受体 2 诱导免疫反应。

A novel exopolysaccharide from the biofilm of Thermus aquaticus YT-1 induces the immune response through Toll-like receptor 2.

机构信息

From the Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.

出版信息

J Biol Chem. 2011 May 20;286(20):17736-45. doi: 10.1074/jbc.M110.200113. Epub 2011 Mar 28.

Abstract

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-α 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.

摘要

细菌多糖已知可诱导巨噬细胞的免疫反应。在这里,我们从水生栖热菌 YT-1 的生物膜中分离出一种新型胞外多糖,并评估了其结构和免疫调节作用。这种多糖 TA-1 的大小通过排阻色谱法推断为 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 的新型结构。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,并且缺乏酸性糖。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 在其免疫活性中的天然受体是 TLR2。TLR2 对 TA-1 的识别通过 TA-1 诱导野生型小鼠腹腔巨噬细胞而不是 TLR2(-/-) 小鼠产生 IL-6 得到证实。作为 TLR2 激动剂的 TA-1 可能可用作佐剂,并能增强细胞因子释放,从而增强免疫反应。此外,TA-1 诱导细胞因子释放依赖于 MyD88/TIRAP。

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