Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus.
Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus.
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DOI：
10.1016/j.immuni.2014.06.015
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发表时间：
2014-08-21
期刊：
影响因子：
32.4
通讯作者：
Cadwell, Ken
中科院分区：
文献类型：
--
作者：
Ramanan, Deepshika;Tang, Mei San;Bowcutt, Rowann;Loke, P'ng;Cadwell, Ken
Nod2被广泛认为是一种细菌传感器，可诱导抗菌和炎症基因表达程序。因此，目前尚不清楚为什么破坏细菌识别的Nod2突变矛盾地成为克罗恩病的最高危险因素之一，克罗恩病涉及针对肠道细菌的夸大免疫反应。在这里，我们发现了Nod2 - / -小鼠小肠上皮的几种异常，包括炎症基因表达和杯状细胞功能障碍，这些异常与上皮内淋巴细胞和Myd88活性产生过量的干扰素-γ有关。值得注意的是，这些异常依赖于肠道微生物群中常见成员——普通杆菌（Bacteroides vulgatus）的扩张，后者也介导了小肠损伤后Nod2 - / -小鼠炎症的加剧。这些结果表明，Nod2通过控制微生物群来预防炎症病理，并支持涉及特定基因-微生物相互作用的多打击疾病模型。
Nod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt bacterial recognition are paradoxically among the highest risk factors for Crohn’s disease, which involves an exaggerated immune response directed at intestinal bacteria. Here, we identified several abnormalities in the small intestinal epithelium of Nod2−/− mice including inflammatory gene expression and goblet cell dysfunction, which were associated with excess interferon-γ production by intraepithelial lymphocytes and Myd88 activity. Remarkably, these abnormalities were dependent on the expansion of a common member of the intestinal microbiota, Bacteroides vulgatus, which also mediated exacerbated inflammation in Nod2−/− mice upon small intestinal injury. These results indicate that Nod2 prevents inflammatory pathologies by controlling the microbiota, and support a multi-hit disease model involving specific gene-microbe interactions.
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29.4
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影响因子：
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