Mans Jeffrey J, Lamont Richard J, Handfield Martin
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
Infect Disord Drug Targets. 2006 Sep;6(3):299-309. doi: 10.2174/187152606778249926.
Host-pathogen interactions are inherently complex and dynamic. The recent use of human microarrays has been invaluable to monitor the effects of various bacterial and viral pathogens upon host cell gene expression programs. This methodology has allowed the host response transcriptome of several cell lines to be studied on a global scale. To this point, the great majority of reports have focused on the response of immune cells, including macrophages and dendritic cells. These studies revealed that the immune response to microbial pathogens is tailored to different microbial challenges. Conversely, the paradigm for epithelial cells has--until recently--held that the epithelium mostly served as a relatively passive physical barrier to infection. It is now generally accepted that the epithelial barrier contributes more actively to signaling events in the immune response. In light of this shift, this review will compare transcriptional profiling data from studies that involved host-pathogen interactions occurring with epithelial cells. Experiments that defined both a common core response, as well as pathogen-specific host responses will be discussed. This review will also summarize the contributions that transcriptional profiling analysis has made to our understanding of bacterial physio-pathogensis of infection. This will include a discussion of how host transcriptional responses can be used to infer the function of virulence determinants from bacterial pathogens interacting with epithelial mucosa. In particular, we will expand upon the lessons that have been learned from gastro-intestinal and oral pathogens, as well as from members of the commensal flora.
宿主与病原体的相互作用本质上是复杂且动态的。近期人类微阵列的应用对于监测各种细菌和病毒病原体对宿主细胞基因表达程序的影响具有极高价值。这种方法使得对几种细胞系的宿主反应转录组进行全球规模的研究成为可能。至此,绝大多数报告都聚焦于免疫细胞的反应,包括巨噬细胞和树突状细胞。这些研究表明,对微生物病原体的免疫反应是针对不同的微生物挑战进行调整的。相反,直到最近,上皮细胞的范例一直认为上皮主要作为对感染相对被动的物理屏障。现在人们普遍认为,上皮屏障在免疫反应的信号事件中发挥更积极的作用。鉴于这种转变,本综述将比较涉及上皮细胞发生的宿主 - 病原体相互作用的研究中的转录谱数据。将讨论定义了共同核心反应以及病原体特异性宿主反应的实验。本综述还将总结转录谱分析对我们理解细菌感染的生理病理学所做的贡献。这将包括讨论如何利用宿主转录反应来推断与上皮黏膜相互作用的细菌病原体毒力决定因素的功能。特别是,我们将详细阐述从胃肠道和口腔病原体以及共生菌群成员中学到的经验教训。