Galindo Cristi L, Moen Scott T, Kozlova Elena V, Sha Jian, Garner Harold R, Agar Stacy L, Chopra Ashok K
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Comp Funct Genomics. 2009;2009:914762. doi: 10.1155/2009/914762. Epub 2010 Jan 20.
We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT) Y. pestis CO92 and its Braun lipoprotein (Deltalpp) mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Deltalpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS-) associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague.
我们使用小鼠基因芯片来描绘在野生型（WT）鼠疫耶尔森菌CO92及其毒力降低的布劳恩脂蛋白（Deltalpp）突变体的小鼠肺鼠疫感染模型中肝脏、肺和脾脏的全局转录谱。这些器官对野生型鼠疫耶尔森菌感染表现出不同的转录反应，但所有三个组织中受影响的总体宿主功能过程相似。在炎症、细胞因子信号传导和凋亡细胞死亡相关基因中发现了基因表达改变。野生型和Deltalpp突变体感染小鼠的比较表明，脂多糖（LPS）相关基因表达存在显著重叠，但Lpp的缺失在关键调节节点扰乱了宿主细胞信号传导，导致免疫反应改变并可能导致宿主细胞凋亡。我们生成了一个包含主要炎症成分的假定信号通路，该通路可以解释LPS和Lpp的协同作用，并为鼠疫耶尔森菌在小鼠肺鼠疫模型中缺失lpp基因导致的减毒提供了机制基础。
