Differential release and distribution of Nod1 and Nod2 immunostimulatory molecules among bacterial species and environments
Differential release and distribution of Nod1 and Nod2 immunostimulatory molecules among bacterial species and environments
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DOI：
10.1074/jbc.m602638200
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发表时间：
2006-09-29
影响因子：
4.8
通讯作者：
Inohara, Naohiro
中科院分区：
文献类型：
--
作者：
Hasegawa, Mizuho;Yang, Kangkang;Inohara, Naohiro
Nod1和Nod2是参与识别细菌分子的细胞内蛋白，它们的遗传变异与受环境因素强烈影响的几种炎症性疾病有关。然而，Nod1和Nod2刺激分子在不同细菌物种和环境中的分布是未知的。在这里，我们建立了一个定量的生物测定筛选和表征Nod1和Nod2刺激活性在不同的环境网站和细菌物种。使用这个系统，我们发现，包括食物和土壤在内的常见环境中含有高水平的Nod1和Nod2刺激活性。几种芽孢杆菌被确定为具有最高的Nod1刺激活性的土壤细菌。与其他免疫刺激分子不同，在培养上清液中发现了较高水平的Nod1刺激活性，而不是在全细胞细菌的提取物中。Nod1刺激分子在极端pH和沸腾条件下高度稳定，并以酰胺酶和sltY独立的方式合成。这些结果表明，存在于环境中的细菌通过Nod1刺激宿主免疫系统的新机制。
Nod1 and Nod2 are intracellular proteins that are involved in recognition of bacterial molecules and their genetic variations have been linked to several inflammatory diseases that are strongly affected by environmental factors. However, the distribution of Nod1- and Nod2-stimulatory molecules in different bacterial species and environments is unknown. Here we established a quantitative bioassay to screen and characterize Nod1 and Nod2-stimulatory activities in different environmental sites and bacterial species. Using this system, we found that common environments including foods and soils contain high levels of Nod1- and Nod2-stimulatory activities. Several Bacillus species were identified to possess the highest Nod1- stimulatory activity among soil bacteria. Unlike other immunostimulatory molecules, the higher level of Nod1- stimulatory activity was found in the culture supernatant and not in extracts from whole cell bacteria. Nod1- stimulatory molecules were highly stable at extreme pH and boiling conditions and were synthesized in an amidase- and sltY-independent manner. These results suggest a novel mechanism by which bacteria present in the environment stimulate the host immune system through Nod1.