Khaniya Bina, Almeida Luciane, Basu Urmila, Taniguchi Masaaki, Williams John L, Barreda Daniel R, Moore Stephen S, Guan Le Luo
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
J Toxicol Environ Health A. 2009;72(17-18):1008-13. doi: 10.1080/15287390903084199.
The most likely route of entry of infection following oral exposure to transmissible spongiform encephalopathies (TSE) is via the immunologically active Peyer's patches (PP). These secondary lymphoid organs appear to be the potential route for prion neuroinvasion. However, the molecular mechanisms involved in the uptake of the infectious prion agent and progression of disease remain still unclear. This investigation examined the changes in gene expression in PP following oral exposure of cattle to bovine spongiform encephalopathy (BSE) agents. The gene expression patterns in PP from cows 12 mo after BSE challenge were compared with controls using a microarray platform containing 24,000 oligonucleotides representing 16,846 unique gene loci and 5943 Expressed Sequence Tag (EST) from bovine genome. Between the challanged and control animals, 90 genes and 16 EST were identified as significantly differentially, expressed (>2.0-fold change): 36 were upregulated and 70 were downregulated. Of these genes, five were found to be related to immune function. Major histocompatibility complex (MHC) class II, MHC class II DQ alpha, L-RAP, and two hypothetical proteins. Differentially expressed genes related to cellular and metabolic processes including development and maturation of cells in the PP were also identified. In this context, the potential impacts of these gene expression changes in PP on BSE development are discussed.
经口接触传染性海绵状脑病(TSE)后,最可能的感染途径是通过具有免疫活性的派尔集合淋巴结(PP)。这些二级淋巴器官似乎是朊病毒神经侵袭的潜在途径。然而,感染性朊病毒因子的摄取及疾病进展所涉及的分子机制仍不清楚。本研究检测了牛经口接触牛海绵状脑病(BSE)病原体后PP中的基因表达变化。使用一个包含24000个寡核苷酸的微阵列平台,将BSE攻击12个月后奶牛PP中的基因表达模式与对照组进行比较,这些寡核苷酸代表了16846个独特基因位点以及来自牛基因组的5943个表达序列标签(EST)。在受攻击动物和对照动物之间,90个基因和16个EST被鉴定为有显著差异表达(变化>2.0倍):36个上调,70个下调。在这些基因中,发现有5个与免疫功能相关。主要组织相容性复合体(MHC)II类、MHC II类DQα、L-RAP以及两种假定蛋白。还鉴定出了与细胞和代谢过程相关的差异表达基因,包括PP中细胞的发育和成熟。在此背景下,讨论了PP中这些基因表达变化对BSE发展的潜在影响。