Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG.
Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG.
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DOI：
10.1186/1475-2859-11-161
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发表时间：
2012-12-15
影响因子：
6.4
通讯作者：
Lebeer S
中科院分区：
文献类型：
--
作者：
Claes IJ;Segers ME;Verhoeven TL;Dusselier M;Sels BF;De Keersmaecker SC;Vanderleyden J;Lebeer S
益生菌越来越多地用作免疫调节剂。然而，关于这些细菌的免疫调节分子的详细分子知识仍然落后。脂磷壁酸（LTA）被认为是革兰氏阳性菌的主要微生物相关分子模式（MAMP）。然而，关于其免疫信号传导能力的许多细节和定量数据仍然未知，特别是在有益细菌中。最近，我们已经证明，与野生型相比，具有修饰的LTA分子的模型益生菌鼠李糖乳杆菌GG（LGG）的dltD突变体在DSS诱导的结肠炎模型中具有增强的益生菌功效。在这项研究中，在体外研究了D-丙氨酰化和酰化LTA对LGG促炎活性的重要性。纯化的LGG野生型天然LTA在与TLR 2/6相互作用后，在HEK 293 T细胞中表现出浓度依赖性的NF-κB信号转导激活，但不与单独的TLR 2相互作用。LTA的化学脱酰作用干扰了TLR 2/6相互作用，而化学脱酰作用则观察到中等程度的影响。类似地，与野生型相比，LGG的dltD突变体在HEK 293 T报告细胞系中表现出显著降低的激活TLR 2/6依赖性NF-κB信号传导的能力。此外，与野生型相比，LGG的dltD突变体显示Caco-2上皮细胞系中趋化因子IL-8 mRNA的诱导减少。用高度纯化的LGG的LTA进行的实验证实，LTA是Caco-2上皮细胞中IL-8 mRNA诱导的关键因子。化学脱烷基化和脱酰化降低IL-8 mRNA表达。总之，我们的结果表明LGG的LTA是一种重要的MAMP，具有促炎活性，例如通过TLR 2/6相互作用在肠上皮细胞中诱导IL-8和在HEK 293 T细胞中诱导NF-κB。这些活性需要LGG LTA的脂质链，而D-丙氨酸取代基也很重要，特别是对于Caco-2细胞中的IL-8诱导。
Probiotic bacteria are increasingly used as immunomodulatory agents. Yet detailed molecular knowledge on the immunomodulatory molecules of these bacteria is lagging behind. Lipoteichoic acid (LTA) is considered a major microbe-associated molecular pattern (MAMP) of Gram-positive bacteria. However, many details and quantitative data on its immune signalling capacity are still unknown, especially in beneficial bacteria. Recently, we have demonstrated that a dltD mutant of the model probiotic Lactobacillus rhamnosus GG (LGG), having modified LTA molecules, has an enhanced probiotic efficacy in a DSS-induced colitis model as compared to wild-type. In this study, the importance of D-alanylated and acylated LTA for the pro-inflammatory activity of LGG was studied in vitro. Purified native LTA of LGG wild-type exhibited a concentration-dependent activation of NF-κB signalling in HEK293T cells after interaction with TLR2/6, but not with TLR2 alone. Chemical deacylation of LTA interfered with the TLR2/6 interaction, while a moderate effect was observed with chemical dealanylation. Similarly, the dltD mutant of LGG exhibited a significantly reduced capacity to activate TLR2/6-dependent NF-κB signalling in a HEK293T reporter cell line compared to wild-type. In addition, the dltD mutant of LGG showed a reduced induction of mRNA of the chemokine IL-8 in the Caco-2 epithelial cell line compared to wild-type. Experiments with highly purified LTA of LGG confirmed that LTA is a crucial factor for IL-8 mRNA induction in Caco-2 epithelial cells. Chemical dealanylation and deacylation reduced IL-8 mRNA expression. Taken together, our results indicate that LTA of LGG is a crucial MAMP with pro-inflammatory activities such as IL-8 induction in intestinal epithelial cells and NF-κB induction in HEK293T cells via TLR2/6 interaction. The lipid chains of LGG LTA are needed for these activities, while also the D-alanine substituents are important, especially for IL-8 induction in Caco-2 cells.
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影响因子：
24.5
作者：
Prantera, C;Scribano, ML;Luzi, C
通讯作者：
Luzi, C
影响因子：
6.4
作者：
Dessing, Mark C.;Schouten, Marcel;van der Poll, Tom
通讯作者：
van der Poll, Tom
影响因子：
2.4
作者：
Schultz M;Timmer A;Herfarth HH;Sartor RB;Vanderhoof JA;Rath HC
通讯作者：
Rath HC
影响因子：
4.4
作者：
Lebeer, Sarah;Claes, Ingmar;Vanderleyden, Jos
通讯作者：
Vanderleyden, Jos
影响因子：
3.1
作者：
Morath, S;Geyer, A;Hartung, T
通讯作者：
Hartung, T