Zhang Jay
Genomics Research Centre, Griffith Health Institute, Gold Coast Campus, Griffith University, Southport, Queensland, Australia.
PLoS One. 2013 Jun 18;8(6):e65128. doi: 10.1371/journal.pone.0065128. Print 2013.
Mycobacterium tuberculosis (MTB) infects an estimated one-third of the global population and is one of the main causes of mortality from an infectious agent. The characteristics of macrophages challenged by MTB with a high multiplicity of infection (MOI), which mimics both clinical disseminated infection and granuloma formation, are distinct from macrophages challenged with a low MOI. To better understand the cross talk between macrophage host cells and mycobacteria, we compared the transcription patterns of mouse macrophages infected with bacille Calmette-Guérin, H37Ra and M. smegmatis. Attention was focused on the changes in the abundance of transcripts related to immune system function. From the results of a transcriptome profiling study with a high mycobacterial MOI, we defined a pathogen-specific host gene expression pattern. The present study suggests that two integrins, ITGA5 and ITGAV, are novel cell surface receptors mediating mycobacterium entry into macrophages challenged with high MOI. Our results indicate that SRC likely plays a central role in regulating multiple unique signaling pathways activated by MTB infection. The integrated results increase our understanding of the molecular networks behind the host innate immune response and identify important targets that might be useful for the development of tuberculosis therapy.
结核分枝杆菌（MTB）感染了全球约三分之一的人口，是由感染因子导致死亡的主要原因之一。受到高感染复数（MOI）的MTB攻击的巨噬细胞的特征，既模拟了临床播散性感染又模拟了肉芽肿形成，与受到低MOI攻击的巨噬细胞不同。为了更好地理解巨噬细胞宿主细胞与分枝杆菌之间的相互作用，我们比较了感染卡介苗、H37Ra和耻垢分枝杆菌的小鼠巨噬细胞的转录模式。重点关注与免疫系统功能相关的转录本丰度的变化。从一项高分枝杆菌MOI的转录组分析研究结果中，我们定义了一种病原体特异性的宿主基因表达模式。本研究表明，两种整合素ITGA5和ITGAV是介导分枝杆菌进入受到高MOI攻击的巨噬细胞的新型细胞表面受体。我们的结果表明，SRC可能在调节由MTB感染激活的多个独特信号通路中起核心作用。综合结果增进了我们对宿主固有免疫反应背后分子网络的理解，并确定了可能对结核病治疗开发有用的重要靶点。
