Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects
Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects
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DOI：
10.1016/j.imbio.2008.02.001
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发表时间：
2008-01-01
期刊：
影响因子：
2.8
通讯作者：
Schrezenmeir, Juergen
中科院分区：
文献类型：
--
作者：
Ghadimi, Darab;Foelster-Holst, Regina;Schrezenmeir, Juergen
在过敏性疾病患病率增加的潜在因素中，已经提出了肠道植物群的改变或儿童期缺乏微生物暴露。TH 2-细胞因子增加IgE的产生并刺激肥大细胞和嗜酸性粒细胞，而T（H）1-细胞因子，例如Lis IFN-γ，可以抑制IgE合成并刺激伊加分泌片段的表达。因此，T（H）1-和T（H）2-细胞因子表达的失调可能有助于过敏性疾病的发生和维持。据报道，属于天然肠道微生物区系的乳酸杆菌可降低特应性皮炎的发病率和过敏表现的严重程度，并调节T（H）1/T（H）2反应。我们试图评估不同益生菌，鼠李糖乳杆菌GG、加氏乳杆菌（PA 16/8）、两歧双歧杆菌（MP 20/5）和长双歧杆菌（SP 07/3）的作用，对外周血单个核细胞（PBMC）的T（H）1 I和T（H）2应答的影响从健康受试者和从对屋尘螨过敏的患者到葡萄球菌肠毒素A（SEA）和屋尘螨（Dpt）。为了阐明这些效应的分子基础，将细菌基因组DNA的效应与活细菌的效应进行了比较。将来自过敏性患者和来自健康供体的PBMC分别在有或没有SEA和Dpt过敏原的情况下孵育24或48小时。通过测量T（H）1/T（H）2-细胞因子的产生来评估与活益生菌预孵育的效果以及它们的基因组DNA同时盖到培养物中并孵育24小时的效果。所测试的活革兰氏阳性益生菌及其基因组DNA抑制SEA和Dpt刺激的T（H）2-细胞因子（IL-4和IL-5）的分泌，并增强IFN-γ的刺激。这种作用是剂量依赖性的，具有最佳剂量，这对于所有测试的乳酸产生细菌（LAB）（10个细菌/PBMC）及其DNA（75 ng/ml）是相同的。基于LAB及其DNA所达到的最大效果，超过50%的效果似乎是由DNA贡献的。对照革兰氏阴性大肠杆菌TG 1没有诱导显着作用。乳酸杆菌和双歧杆菌减少SEA刺激的IL-4和IL-5的生产更有效地从健康受试者比过敏患者的PBMC。与此相反，Dpt刺激的IL-4-和IL-5-分泌的抑制在来自过敏受试者的细胞中更明显。与活的LAB相比，细菌DNA以类似的方式抑制IL-4-和IL-5-的分泌。SEA-和更重要的是，Dpt-刺激的IFN-γ刺激在过敏性受试者中比在健康受试者中更不明显，而IFN-γ刺激在过敏性受试者中更明显。测试的益生菌以及它们的基因组DNA调节T（H）1/T（H）2对某些过敏原的剂量依赖性反应。在这种体外模型中，DNA似乎对活细菌所产生的作用有50%的贡献。益生菌作用的大小在健康受试者和过敏受试者之间不同。对于测试菌株发现的调节是否可能用于预防和治疗过敏性疾病，必须在临床试验中进行评估。(C)2008年由Elsevier GmbH出版。
Among the factors potentially involved in the increased prevalence of allergic diseases, modification of the intestinal flora or lack of microbial exposure during childhood has been proposed. TH2-cytokines increase the production of IgE and stimulate mast cells and eosinophils, whereas T(H)1-cytokines, Such Lis IFN-gamma, may suppress IgE synthesis and Stimulate the expression of the secretory piece of IgA. Thus, a dysregulation In the expression of T(H)1- and T(H)2-cytokines may contribute to the initiation and maintenance of allergic diseases. Lactobacilli belonging to the natural intestinal rnicroflora were reported to reduce the incidence of atopic dermatitis and the severity of allergic manifestations and to modulate T(H)1/T(H)2 responses. The mechanisms still remain to be elucidated.We Sought to assess the effect of different probiotics, Lactobacillus rhamnosus GG, Lactobacillus gasseri (PA 16/8) Bifidobacterium bifidum (MP20/5), and B Bifidobacterium longum (SP07/3), on the T(H)1 I and T(H)2 responses of peripheral blood mononuclear cells (PBMCs) from healthy subjects and from patients with allergy against house dust mite to Staphylococcus enterotoxin A (SEA) and Dermatophagoides pteronyssinus (Dpt). To elucidate the Molecular basis of these effects, the effects of bacterial genomic DNA were compared with the effects of viable bacteria. PBMCs from allergic patients and from healthy donors were incubated for 24 or 48h, respectively, With Or Without SEA and Dpt allergens. The effects of preincubation with live probiotic bacteria and the effect of their genomic DNA, Lidded Simultaneously to Cultures and incubated for 24h, were assessed by measuring T(H)1/T(H)2-cytokine production.The tested live Gram-positive probiotic bacteria and their genomic DNA inhibited SEA- and Dpt-stimulated secretion of T(H)2-cytokines (IL-4 and IL-5) and enhanced the Stimulation of IFN-gamma. This effect was dose-dependent with a dosage-optimum, which was identical for all lactic acid producing bacteria (LAB) tested (10 bacteria per (PBMC) and their DNA (75 ng/rnl). Based on the maximal effects achieved with LAB and their DNA, more than 50% of the effects seem to be contributed by DNA. No significant effect was induced by the control, Gram-negative Escherichia coli TGl. Lactobacilli and bifidobacteria reduced SEA-stimulated IL-4 and IL-5 production more effectively in PBMCs from healthy subjects than from allergic patients. In contrast to this, inhibition of Dpt-stimulated IL-4- and IL-5-secretion was more pronounced in cells from allergic subjects. Compared with living LAB, bacterial DNA inhibited IL-4- and IL-5-secretion in a similar manner. SEA- and even more so Dpt-stimulated IFN-gamma stimulation by living LAB was less pronounced in allergic than in healthy Subjects, whereas IFN-gamma Stimulation by their DNA was more Pronounced in allergic subjects.The tested probiotic bacteria as well as their genomic DNA modulated the T(H)1/T(H)2 response to some allergens dose-dependently. DNA seems to contribute to 50% of the effect exerted by living bacteria in this in vitro model. The magnitude of the probiotic effects differed between healthy and allergic subjects. Whether the modulation found for the tested strains might be useful for the prevention and treatment of allergic diseases has to be assessed In clinical trials. (C) 2008 Published by Elsevier GmbH.