Kierstein S, Noyes H, Naessens J, Nakamura Y, Pritchard C, Gibson J, Kemp S, Brass A
International Livestock Research Institute, Nairobi, Kenya.
Genes Immun. 2006 Dec;7(8):667-79. doi: 10.1038/sj.gene.6364345. Epub 2006 Oct 26.
This study aimed to provide the foundation for an integrative approach to the identification of the mechanisms underlying the response to infection with Trypanosoma congolense, and to identify pathways that have previously been overlooked. We undertook a large-scale gene expression analysis study comparing susceptible A/J and more tolerant C57BL/6 mice. In an initial time course experiment, we monitored the development of parasitaemia and anaemia in every individual. Based on the kinetics of disease progression, we extracted total RNA from liver at days 0, 4, 7, 10 and 17 post infection and performed a microarray analysis. We identified 64 genes that were differentially expressed in the two strains in non-infected animals, of which nine genes remained largely unaffected by the disease. Gene expression profiling at stages of low, peak, clearance and recurrence of parasitaemia suggest that susceptibility is associated with high expression of genes coding for chemokines (e.g. Ccl24, Ccl27 and Cxcl13), complement components (C1q and C3) and interferon receptor alpha (Ifnar1). Additionally, susceptible A/J mice expressed higher levels of some potassium channel genes. In contrast, messenger RNA levels of a few immune response, metabolism and protease genes (e.g. Prss7 and Mmp13) were higher in the tolerant C57BL/6 strain as compared to A/J.
本研究旨在为综合方法奠定基础,以确定冈比亚锥虫感染反应背后的机制,并识别此前被忽视的途径。我们进行了一项大规模基因表达分析研究,比较了易感的A/J小鼠和耐受性更强的C57BL/6小鼠。在最初的时间进程实验中,我们监测了每只个体的寄生虫血症和贫血的发展情况。根据疾病进展的动力学,我们在感染后第0、4、7、10和17天从肝脏中提取总RNA,并进行了微阵列分析。我们鉴定出64个在未感染动物的两种品系中差异表达的基因,其中9个基因在很大程度上不受疾病影响。在寄生虫血症的低水平、高峰期、清除期和复发期的基因表达谱表明,易感性与编码趋化因子(如Ccl24、Ccl27和Cxcl13)、补体成分(C1q和C3)和干扰素受体α(Ifnar1)的基因的高表达有关。此外,易感的A/J小鼠表达了更高水平的一些钾通道基因。相比之下,与A/J相比,耐受性C57BL/6品系中一些免疫反应、代谢和蛋白酶基因(如Prss7和Mmp13)的信使RNA水平更高。