Dose-dependent immunomodulation of human dendritic cells by the probiotic Lactobacillus rhamnosus Lcr35.
Dose-dependent immunomodulation of human dendritic cells by the probiotic Lactobacillus rhamnosus Lcr35.
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DOI：
10.1371/journal.pone.0018735
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发表时间：
2011-04-18
期刊：
影响因子：
3.7
通讯作者：
Forestier C
中科院分区：
文献类型：
--
作者：
Evrard B;Coudeyras S;Dosgilbert A;Charbonnel N;Alamé J;Tridon A;Forestier C
免疫系统对益生菌的反应仍然存在争议。一些菌株在体外调节树突状细胞（dc）的细胞因子产生并诱导调节反应，而另一些菌株则相反地诱导促炎反应。这些菌株依赖效应被认为与细菌和模式识别受体之间的特定相互作用有关。我们研究了一种特性良好的益生菌菌株鼠李糖乳杆菌Lcr35对人类单核细胞来源的未成熟树突状细胞的影响，使用了广泛的细菌浓度（感染的多重性，MOI，从0.01到100）。DNA微阵列和qRT-PCR分析显示，益生菌诱导了基因表达的大规模变化（近1700个基因被调节，变化幅度为3倍），但仅在高剂量下（MOI, 100）。上调的基因主要参与免疫应答，并根据Torri模型确定了炎症的分子特征。流式细胞术分析还揭示了DC膜表型成熟的剂量依赖性，直到DC达到半成熟状态，CD86, CD83， HLA-DR和TLR4的膜表达上调，DC- sign， MR和CD14的下调。dc分泌的细胞因子检测显示，Lcr35诱导前th1 /Th17细胞因子（TNFα、IL-1β、IL-12p70、IL-12p40和IL-23）水平呈剂量依赖性升高，但IL-10浓度仅小幅升高。因此，益生菌L. rhamnosus Lcr35诱导人dc的剂量依赖性免疫调节，导致高剂量的细胞半成熟和强烈的促炎作用。这些结果有助于更全面地了解这种益生菌的作用机制，从而了解其治疗感染性或ige依赖性过敏性疾病的潜在临床适应症。
The response of the immune system to probiotics remains controversial. Some strains modulate the cytokine production of dendritic cells (DCs) in vitro and induce a regulatory response, while others induce conversely a pro-inflammatory response. These strain-dependent effects are thought to be linked to specific interactions between bacteria and pattern recognition receptors. We investigated the effects of a well characterized probiotic strain, Lactobacillus rhamnosus Lcr35, on human monocyte-derived immature DCs, using a wide range of bacterial concentrations (multiplicity of infection, MOI, from 0.01 to 100). DNA microarray and qRT-PCR analysis showed that the probiotic induced a large-scale change in gene expression (nearly 1,700 modulated genes, with 3-fold changes), but only with high doses (MOI, 100). The upregulated genes were mainly involved in immune response and identified a molecular signature of inflammation according to the model of Torri. Flow cytometry analysis also revealed a dose-dependent maturation of the DC membrane phenotype, until DCs reached a semi-mature state, with an upregulation of the membrane expression of CD86, CD83, HLA-DR and TLR4, associated with a down-regulation of DC-SIGN, MR and CD14. Measurement of the DC-secreted cytokines showed that Lcr35 induced a strong dose-dependent increase of the pro-Th1/Th17 cytokine levels (TNFα, IL-1β, IL-12p70, IL-12p40 and IL-23), but only a low increase in IL-10 concentration. The probiotic L. rhamnosus Lcr35 therefore induce a dose-dependent immunomodulation of human DCs leading, at high doses, to the semi-maturation of the cells and to a strong pro-inflammatory effect. These results contribute to a fuller understanding of the mechanism of action of this probiotic, and thus of its potential clinical indications in the treatment of either infectious or IgE-dependent allergic diseases.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
DOI：
10.1073/pnas.0500098102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Mohamadzadeh, M;Olson, S;Klaenhammer, TR
通讯作者：
Klaenhammer, TR
影响因子：
4.4
作者：
Christensen, HR;Frokiær, H;Pestka, JJ
通讯作者：
Pestka, JJ
影响因子：
3.8
作者：
Dogi, C. A.;Galdeano, C. Maldonado;Perdigon, Gabriela
通讯作者：
Perdigon, Gabriela
影响因子：
2
作者：
Fang, Shiuh-Bin;Lee, Hung-Chang;Fang, Hsu-Wei
通讯作者：
Fang, Hsu-Wei