深度测序技术分析小鼠巨噬细胞感染布鲁菌16M株的转录组学变化

Deep sequenceing-based on early transcriptome analysis of the RAW264.7 cell with the Brucella melitensis 16M infection

布鲁菌病是由布鲁菌引起的一种人兽共患性传染病,曾被用作生物恐怖战剂。本研究利用深度测序技术对布鲁菌感染小鼠巨噬细胞RAW264.7的转录组学轮廓进行了描述。在感染后4 h,筛选出差异表达基因3 576个,其中58%的基因表现上调;在感染后24 h,筛选出差异表达基因3 962个,其中45%的基因表现上调。并且在感染后24 h内,变化显著的基因都是与炎症、免疫、吞噬、凋亡紧密相关的。进而我们分析了在感染后24 h内显著变化的代谢途径,这些代谢途径包括内质网代谢途径、溶酶体代谢途径、及与凋亡相关的代谢途径;及被显著富集的信号通路,这些信号通路包括凋亡通路、NOD受体信号通路、FcγR介导的吞噬通路、溶酶体信号通路、p53信号通路、内质网相关蛋白的通路;并且发现B细胞受体和toll样受体信号通路在感染后24 h与感染后4 h相比被显著富集。本研究建立的巨噬细胞感染布鲁菌后差异表达基因数据库,将为布鲁菌致病机制的逐步阐述奠定基础。

Brucellosis, which is caused by Brucella,is a worldwide zoonotic infectious disease and it was used as a biological terrorist. In current study,the kinetic transcriptional profile of gene expression in macrophages infected with the Brucella melitensis strain 16M was investigated using a technology based on deep sequencing. There are 3576 genes expressed significantly difference at 4 h postinfection,approximately 58% genes expression was up-regulated. The genes differently expressed are closely related to inflammatory,immunity, engulfed and apotosis, so we analyzed the pathways significantly changed at 4 h postinfection, which include apoptosis pathway, lysosome pathway, NODlike receptor signaling pathway, Fc gamma R-mediated phagocytosis, p53 signaling pathway, and protein processing in the endoplasmic reticulum pathway. The database, which differently expressed genes of macrophage cell infected with Brucella,would provide the basis for evaluating the role of host during the infection.