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益生菌对人树突状细胞中IL-10/IL-12轴的调节作用

Regulation of the IL-10/IL-12 axis in human dendritic cells with probiotic bacteria.

作者信息

Gad Monika, Ravn Peter, Søborg Ditte A, Lund-Jensen Karina, Ouwehand Arthur C, Jensen Simon S

机构信息

Bioneer A/S, Kogle Allé 2, Hørsholm, Denmark.

出版信息

FEMS Immunol Med Microbiol. 2011 Oct;63(1):93-107. doi: 10.1111/j.1574-695X.2011.00835.x. Epub 2011 Jul 26.

Abstract

In this study, we have used monocyte-derived dendritic cells (DCs) to design a screening model for the selection of microorganisms with the ability to suppress DC-secreted IL-12p70, a critical cytokine for the induction of T-helper cell type 1 immune responses under inflammatory conditions. By the treatment of DCs with cocktails containing TLR agonists and proinflammatory cytokines, the cells increased the secretion of the Th1-promoting cytokine IL-12p70. Clinically used probiotics were tested for their IL-10- and IL-12p70-stimulating properties in immature DCs, and showed a dose-dependent change in the IL-10/IL-12p70 balance. Lactobacillus acidophilus NCFM(™) and the probiotic mixture VSL#3 showed a strong induction of IL-12p70, whereas Lactobacillus salivarius Ls-33 and Bifidobacterium infantis 35624 preferentially induced IL-10. Escherichia coli Nissle 1917 induced both IL-10 and IL-12p70, whereas the probiotic yeast Saccharomyces boulardii induced low levels of cytokines. When combining these microorganisms with the Th1-promoting cocktails, E. coli Nissle 1917 and B. infantis 35624 were potent suppressors of IL-12p70 secretion in an IL-10-independent manner, indicating a suppressive effect on Th1-inducing antigen-presenting cells. The present model, using cocktail-stimulated DCs with potent IL-12p70-stimulating capacity, may be used as an efficient tool to assess the anti-inflammatory properties of microorganisms for potential clinical use.

摘要

在本研究中,我们利用单核细胞衍生的树突状细胞(DCs)设计了一种筛选模型,用于筛选具有抑制DC分泌IL-12p70能力的微生物。IL-12p70是炎症条件下诱导1型辅助性T细胞免疫反应的关键细胞因子。通过用含有Toll样受体(TLR)激动剂和促炎细胞因子的混合物处理DCs,这些细胞增加了促进Th1的细胞因子IL-12p70的分泌。对临床使用的益生菌在未成熟DCs中刺激IL-10和IL-12p70的特性进行了测试,结果显示IL-10/IL-12p70平衡呈剂量依赖性变化。嗜酸乳杆菌NCFM™和益生菌混合物VSL#3对IL-12p70有强烈诱导作用,而唾液乳杆菌Ls-33和婴儿双歧杆菌35624优先诱导IL-10。大肠杆菌Nissle 1917既诱导IL-10也诱导IL-12p70,而益生菌酵母布拉酵母菌诱导的细胞因子水平较低。当将这些微生物与促进Th1的混合物组合时,大肠杆菌Nissle 1917和婴儿双歧杆菌35624以不依赖IL-10的方式有效抑制IL-12p70的分泌,表明对诱导Th1的抗原呈递细胞有抑制作用。本模型使用具有强大IL-12p70刺激能力的混合物刺激的DCs,可作为评估微生物抗炎特性以用于潜在临床应用的有效工具。

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