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首页> 外文期刊>BMC Genomics >Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling
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Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

机译：通过比较mRNA谱分析揭示了克氏锥虫感染宿主细胞的细胞因子依赖性和非依赖性基因表达变化和细胞周期阻滞

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Background The requirements for growth and survival of the intracellular pathogen Trypanosoma cruzi within mammalian host cells are poorly understood. Transcriptional profiling of the host cell response to infection serves as a rapid read-out for perturbation of host physiology that, in part, reflects adaptation to the infective process. Using Affymetrix oligonucleotide array analysis we identified common and disparate host cell responses triggered by T. cruzi infection of phenotypically diverse human cell types. Results We report significant changes in transcript abundance in T. cruzi-infected fibroblasts, endothelial cells and smooth muscle cells (2852, 2155 and 531 genes respectively; fold-change ≥ 2, p-value T. cruzi-infected fibroblasts and endothelial cells transwell plates were used to distinguish cytokine-dependent and -independent gene expression profiles. This approach revealed the induction of metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding as common themes in T. cruzi-infected cells. In addition, the downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection may impede host cell cycle progression. The observation of impaired cytokinesis in T. cruzi-infected cells, following nuclear replication, confirmed this prediction. Conclusion Metabolic pathways and cellular processes were identified as significantly altered at the transcriptional level in response to T. cruzi infection in a cytokine-independent manner. Several of these alterations are supported by previous studies of T. cruzi metabolic requirements or effects on the host. However, our methods also revealed a T. cruzi-dependent block in the host cell cycle, at the level of cytokinesis, previously unrecognized for this pathogen-host cell interaction.
机译：背景对哺乳动物宿主细胞内细胞内病原体克氏锥虫的生长和存活的要求了解得很少。宿主细胞对感染反应的转录谱分析可作为对宿主生理扰动的快速读取，其部分反映了对感染​​过程的适应性。使用Affymetrix寡核苷酸阵列分析，我们确定了表型多样的人类细胞类型的克鲁氏杆菌感染引起的共同和不同的宿主细胞反应。结果我们报道了克鲁维氏酵母感染的成纤维细胞，内皮细胞和平滑肌细胞的转录丰度有显着变化（分别为2852、2155和531个基因;倍数变化≥2，p值克鲁维氏感染的成纤维细胞和内皮细胞转运平板用于区分依赖细胞因子和不依赖基因的基因表达谱，该方法揭示了与克鲁维氏酵母感染细胞共同的代谢和信号传导途径的诱导，这些途径涉及细胞增殖，氨基酸分解代谢和对伤口的反应。参与有丝分裂细胞周期和细胞分裂的基因的下调预示了克鲁维氏酵母感染可能会阻碍宿主细胞周期进程，核复制后对克鲁维氏酵母感染细胞胞质受损的观察证实了这一预测。和细胞过程被确定为在响应克鲁斯感染的转录水平上显着改变以不依赖细胞因子的方式进行。这些变化中的几种得到了先前关于克鲁氏锥虫代谢需求或对宿主影响的研究的支持。但是，我们的方法还揭示了以前无法识别的病原体-宿主细胞相互作用的胞质分裂水平，在宿主细胞周期中存在了克鲁氏梭菌依赖性块。

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