Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis
Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis
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DOI：
10.1038/nature07450
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发表时间：
2008-11-27
期刊：
影响因子：
64.8
通讯作者：
Eberl, Gerard
中科院分区：
文献类型：
--
作者：
Bouskra, Djahida;Brezillon, Christophe;Eberl, Gerard
肠道内稳态对于从食物中有效提取能量和保护免受病原体侵害至关重要。它的破坏可能导致一系列严重疾病，对公共卫生产生重大影响，例如以自毁肠道免疫为特征的炎症性肠道疾病。然而，调节大型细菌植物群和免疫系统之间平衡的机制仍不清楚。肠淋巴组织产生植物群反应性伊加产生B细胞，包括派尔集合淋巴结和肠系膜淋巴结，以及许多孤立的淋巴滤泡（ILF）（1，2）。在这里，我们表明，来自革兰氏阴性细菌的肽聚糖是必要的，足以诱导小鼠中ILF的发生，通过识别上皮细胞中的NOD 1（核苷酸结合寡聚化结构域包含1）先天受体，和β-防御素3-和CCL 20-介导的信号通过趋化因子受体CCR 6。ILF成熟为大的B细胞簇需要随后通过Toll样受体检测细菌。在缺乏ILF的情况下，肠道细菌群落的组成发生了深刻的变化。我们的研究结果表明，肠道细菌和免疫系统的沟通，通过先天检测系统，以产生适应性淋巴组织和维持肠道内稳态。
Intestinal homeostasis is critical for efficient energy extraction from food and protection from pathogens. Its disruption can lead to an array of severe illnesses with major impacts on public health, such as inflammatory bowel disease characterized by self- destructive intestinal immunity. However, the mechanisms regulating the equilibrium between the large bacterial flora and the immune system remain unclear. Intestinal lymphoid tissues generate flora- reactive IgA- producing B cells, and include Peyer's patches and mesenteric lymph nodes, as well as numerous isolated lymphoid follicles (ILFs)(1,2). Here we show that peptidoglycan from Gram- negative bacteria is necessary and sufficient to induce the genesis of ILFs in mice through recognition by the NOD1 ( nucleotide- binding oligomerization domain containing 1) innate receptor in epithelial cells, and beta-defensin 3- and CCL20- mediated signalling through the chemokine receptor CCR6. Maturation of ILFs into large B- cell clusters requires subsequent detection of bacteria by toll- like receptors. In the absence of ILFs, the composition of the intestinal bacterial community is profoundly altered. Our results demonstrate that intestinal bacterial commensals and the immune system communicate through an innate detection system to generate adaptive lymphoid tissues and maintain intestinal homeostasis.