Global analysis of the eukaryotic pathways and networks regulated by Salmonella typhimurium in mouse intestinal infection in vivo.
Global analysis of the eukaryotic pathways and networks regulated by Salmonella typhimurium in mouse intestinal infection in vivo.
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DOI：
10.1186/1471-2164-11-722
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发表时间：
2010-12-20
期刊：
影响因子：
4.4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Liu X;Lu R;Xia Y;Sun J
沙门氏菌引起的急性肠炎是一个公共卫生问题。众所周知，沙门氏菌感染还会增加炎症性肠道疾病和癌症的风险。因此，重要的是要了解沙门氏菌如何在肠道感染的真核途径中发挥作用。然而，鼠伤寒沙门氏菌在活体肠道粘膜中的整体生理功能尚不清楚。在这项研究中，使用全基因组方法和生物信息学分析相结合的方法来研究小鼠结肠对沙门氏菌的体内遗传反应。重点观察沙门氏菌感染后早期(8h)和晚期(4d)的肠道反应。在芯片上显示的28,000个基因中，我们对小鼠结肠粘膜中的mRNA表达的分析表明，在感染后8小时，总共有856个基因有差异表达。在感染后4天，共有7558个基因差异表达。对芯片数据中的23个差异表达基因进行实时定量聚合酶链式反应。独创性路径分析发现，在感染后8小时内，与差异表达基因相关的最重要的途径是氧化磷酸化，它以线粒体为目标。在感染的晚期，一系列与免疫和炎症反应、增殖和凋亡相关的途径被确定，而氧化磷酸化被关闭。组织学分析证实了沙门氏菌的生物学作用，沙门氏菌通过调节多条信号通路，诱导结肠粘膜处于炎症和增殖的生理状态。大多数代谢相关途径被下调的基因靶向，并观察到代谢途径的一般抑制过程。网络分析支持干扰素-γ和肿瘤坏死因子-α作为免疫/炎症反应的介体，用于宿主对病原体的防御。我们的研究提供了关于小鼠结肠粘膜对鼠伤寒沙门氏菌感染的反应的新的全基因组转录图谱数据。建立这些基因之间相互作用的途径和网络有助于我们了解沙门氏菌感染过程中小鼠结肠中复杂的相互作用，并进一步为动员分子级联来对抗体内沙门氏菌相关的结肠感染提供新的见解。
Acute enteritis caused by Salmonella is a public health concern. Salmonella infection is also known to increase the risk of inflammatory bowel diseases and cancer. Therefore, it is important to understand how Salmonella works in targeting eukaryotic pathways in intestinal infection. However, the global physiological function of Salmonella typhimurium in intestinal mucosa in vivo is unclear. In this study, a whole genome approach combined with bioinformatics assays was used to investigate the in vivo genetic responses of the mouse colon to Salmonella. We focused on the intestinal responses in the early stage (8 hours) and late stage (4 days) after Salmonella infection. Of the 28,000 genes represented on the array, our analysis of mRNA expression in mouse colon mucosa showed that a total of 856 genes were expressed differentially at 8 hours post-infection. At 4 days post-infection, a total of 7558 genes were expressed differentially. 23 differentially expressed genes from the microarray data was further examined by real-time PCR. Ingenuity Pathways Analysis identified that the most significant pathway associated with the differentially expressed genes in 8 hours post-infection is oxidative phosphorylation, which targets the mitochondria. At the late stage of infection, a series of pathways associated with immune and inflammatory response, proliferation, and apoptosis were identified, whereas the oxidative phosphorylation was shut off. Histology analysis confirmed the biological role of Salmonella, which induced a physiological state of inflammation and proliferation in the colon mucosa through the regulation of multiple signaling pathways. Most of the metabolism-related pathways were targeted by down-regulated genes, and a general repression process of metabolic pathways was observed. Network analysis supported IFN-γ and TNF-α function as mediators of the immune/inflammatory response for host defense against pathogen. Our study provides novel genome-wide transcriptional profiling data on the mouse colon mucosa's response to the Salmonella typhimurium infection. Building the pathways and networks of interactions between these genes help us to understand the complex interplay in the mice colon during Salmonella infection, and further provide new insights into the molecular cascade, which is mobilized to combat Salmonella-associated colon infection in vivo.