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Regulation of intestinal immune networks by the DNA motifs from probiotics.

益生菌 DNA 基序对肠道免疫网络的调节。

基本信息

批准号：
11660265
负责人：
KITAZAWA Haruki
金额：
$ 2.3万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660265/
关键词：
Probiotics Cytokine L.bulgaricus mucosal immunity DNA IL-7 Cloning Th1 IFNγ IL-12 ブタ

项目摘要

A great interest has increased concerning the therapeutic and preventive effects of yogurt against several diseases. Lactobacillus delbrueckii ssp. bulgaricus (L.bulgaricus) and Streptococcus thermophilus (S.thermophilus), which are dairy lactic acid bacteria (LAB), has been commonly used in yogurt production in the world. In our recent study, we have been particularly focusing on the DNA from yogurt starter cultures as one of the immunomoduratory factors in the LAB.The present study was conducted to elucidate the immunomoduratory functions of the DNA in the gut. The DNA from L.bulgaricus and S.thermophilus significantly stimulated mitogenic responses to murine peyer's patch cells and induced CD69 on the cells. The active DNA was cloned and the DNA motif, looks like CpG motif, was found in L.bulgaricus NIAI B6. L.bulgaricus NIAI B6 was passed through the M cells and digested by macrophage/dendritic cells result in the stimulation of immune cells by the DNA motif. The binding and ingestion of the DNA motif were demonstrated in peyer's patch cells. The DNA motif augmented induction of Th1 type cytokine (IL-7, IL-12, IL-18, IFNγ) mRNA in peyer's patches. Since swine will be valuable as a human model, swine IL-7 cDNA was isolated from neonatal intestinal epithelium by the RACE methods with designated primers based on the conserved sequences of the other mammalian IL-7. Cytokine producing cells induced by the DNA motif were detected in several immune cells such as B, NK, NKT and Dendritic cells. This study demonstrated that mucosal immunostimulatory DNA motif exist in L.bulgaricus NIAI B6 and proposed that the microorganism is a good candidate of a starter culture for the production of new functional foods, "Bio-Defense Foods".

人们对酸奶对几种疾病的治疗和预防作用越来越感兴趣。德氏乳杆菌汤。保加利亚乳酸菌（L.bulgaricus）和嗜热链球菌（S.thermophilus）是乳酸菌（LAB），在世界酸奶生产中已被广泛使用。在我们最近的研究中，我们特别关注酸奶发酵剂中的DNA作为乳酸菌的免疫调节因子之一。本研究旨在阐明肠道DNA的免疫调节功能。保加利亚芽孢杆菌和嗜热芽孢杆菌的DNA显著刺激小鼠peyer's斑块细胞的有丝分裂反应，并诱导细胞上的CD69。克隆出活性DNA，发现该DNA基序与CpG基序相似。保加利亚芽孢杆菌NIAI B6通过M细胞被巨噬细胞/树突状细胞消化，通过DNA基序刺激免疫细胞。在peyer的斑块细胞中证实了DNA基序的结合和摄取。DNA基序增强诱导Th1型细胞因子（IL-7、IL-12、IL-18、IFNγ） mRNA在peyer斑块中的表达。考虑到猪作为人类模型的价值，采用RACE方法从新生儿肠上皮中分离猪IL-7 cDNA，并根据其他哺乳动物IL-7的保守序列指定引物。在B细胞、NK细胞、NKT细胞和树突状细胞等多种免疫细胞中检测到DNA基序诱导的细胞因子产生细胞。本研究证实保加利亚芽孢杆菌NIAI B6中存在粘膜免疫刺激DNA基序，并提出该微生物是生产新型功能食品“生物防御食品”的良好候选发酵剂。