Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice.

Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice.
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DOI:
10.1186/1471-2172-9-65
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发表时间:
2008-11-06
期刊:
影响因子:
3
通讯作者:
Tlaskalova-Hogenova H
Tlaskalova-Hogenova H
中科院分区:
医学4区
文献类型:
--
作者:
Hrncir T;Stepankova R;Kozakova H;Hudcovic T;Tlaskalova-Hogenova H

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哺乳动物出生时基本上是无菌的,但出生后不久,上皮细胞表面就迅速被数量惊人的细菌定植。最广泛的微生物群落是由远端肠道窝藏。肠道微生物群的数量是我们体细胞和生殖细胞总数的10倍。宿主-微生物群的关系已经发展成为互利的。对无菌小鼠的研究表明,肠道微生物群在免疫系统的发育中起着至关重要的作用。本研究的主要目的是阐明肠道微生物群的存在和含有各种细菌污染物的无菌饮食的质量(通过脂多糖(LPS)含量测定)是否会影响gnotobiotic小鼠免疫系统的成熟。我们已经发现,肠道微生物群的存在以及在较小程度上富含LPS的无菌饮食驱动派伊尔集合淋巴结和肠系膜淋巴结中B和T细胞的扩增。最突出的是肠系膜淋巴结中包括Foxp 3表达T细胞的CD 4 + T细胞的扩增。此外,我们已经观察到肠道微生物群的存在和富含LPS的无菌饮食都影响脾细胞的体外细胞因子谱。肠道微生物群和富含LPS的饮食都会增加白细胞介素-12的产生,并减少白细胞介素-4的产生。此外,肠道微生物群的存在增加了白细胞介素-10和干扰素-γ的产生。我们的数据清楚地表明,不仅活的肠道微生物群,而且无菌饮食中含有的微生物组分(LPS)也刺激免疫系统的发育,扩张和功能。最后,我们想强调的是,应定期测试饲料的组成,特别是在所有的gnotobiotic模型中,因为LPS含量和饲料中存在的其他微生物成分可能会显着改变实验结果。
Mammals are essentially born germ-free but the epithelial surfaces are promptly colonized by astounding numbers of bacteria soon after birth. The most extensive microbial community is harbored by the distal intestine. The gut microbiota outnumber ~10 times the total number of our somatic and germ cells. The host-microbiota relationship has evolved to become mutually beneficial. Studies in germ-free mice have shown that gut microbiota play a crucial role in the development of the immune system. The principal aim of the present study was to elucidate whether the presence of gut microbiota and the quality of a sterile diet containing various amounts of bacterial contaminants, measured by lipopolysaccharide (LPS) content, can influence maturation of the immune system in gnotobiotic mice. We have found that the presence of gut microbiota and to a lesser extent also the LPS-rich sterile diet drive the expansion of B and T cells in Peyer's patches and mesenteric lymph nodes. The most prominent was the expansion of CD4+ T cells including Foxp3-expressing T cells in mesenteric lymph nodes. Further, we have observed that both the presence of gut microbiota and the LPS-rich sterile diet influence in vitro cytokine profile of spleen cells. Both gut microbiota and LPS-rich diet increase the production of interleukin-12 and decrease the production of interleukin-4. In addition, the presence of gut microbiota increases the production of interleukin-10 and interferon-γ. Our data clearly show that not only live gut microbiota but also microbial components (LPS) contained in sterile diet stimulate the development, expansion and function of the immune system. Finally, we would like to emphasize that the composition of diet should be regularly tested especially in all gnotobiotic models as the LPS content and other microbial components present in the diet may significantly alter the outcome of experiments.
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