Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, Aarhus University, Blichers allé 20, P,O, Box 50, DK-8830 Tjele, Denmark.
BMC Genomics. 2011 Feb 28;12:130. doi: 10.1186/1471-2164-12-130.
Bovine mastitis is one of the most costly and prevalent diseases affecting dairy cows worldwide. In order to develop new strategies to prevent Escherichia coli-induced mastitis, a detailed understanding of the molecular mechanisms underlying the host immune response to an E. coli infection is necessary. To this end, we performed a global gene-expression analysis of mammary gland tissue collected from dairy cows that had been exposed to a controlled E. coli infection. Biopsy samples of healthy and infected utter tissue were collected at T = 24 h post-infection (p.i.) and at T = 192 h p.i. to represent the acute phase response (APR) and chronic stage, respectively. Differentially expressed (DE) genes for each stage were analyzed and the DE genes detected at T = 24 h were also compared to data collected from two previous E. coli mastitis studies that were carried out on post mortem tissue.
Nine-hundred-eighty-two transcripts were found to be differentially expressed in infected tissue at T = 24 (P < 0.05). Up-regulated transcripts (699) were largely associated with immune response functions, while the down-regulated transcripts (229) were principally involved in fat metabolism. At T = 192 h, all of the up-regulated transcripts were associated with tissue healing processes. Comparison of T = 24 h DE genes detected in the three E. coli mastitis studies revealed 248 were common and mainly involved immune response functions. KEGG pathway analysis indicated that these genes were involved in 12 pathways related to the pro-inflammatory response and APR, but also identified significant representation of two unexpected pathways: natural killer cell-mediated cytotoxicity pathway (KEGG04650) and the Rig-I-like receptor signalling pathway (KEGG04622).
In E. coli-induced mastitis, infected mammary gland tissue was found to significantly up-regulate expression of genes related to the immune response and down-regulate genes related to fat metabolism. Up to 25% of the DE immune response genes common to the three E. coli mastitis studies at T = 24 h were independent of E. coli strain and dose, cow lactation stage and number, tissue collection method and gene analysis method used. Hence, these DE genes likely represent important mediators of the local APR against E. coli in the mammary gland.
牛乳腺炎是世界范围内影响奶牛的最昂贵和最普遍的疾病之一。为了开发预防大肠杆菌引起的乳腺炎的新策略,有必要深入了解宿主对大肠杆菌感染的免疫反应的分子机制。为此,我们对暴露于受控大肠杆菌感染的奶牛的乳腺组织进行了全基因表达分析。在感染后 24 小时(T = 24 h)和 192 小时(T = 192 h)时,采集健康和感染乳房组织的活检样本,分别代表急性阶段反应(APR)和慢性阶段。分析每个阶段的差异表达(DE)基因,并将 T = 24 h 时检测到的 DE 基因与之前进行的两项关于尸检组织的大肠杆菌乳腺炎研究的数据进行比较。
在 T = 24 时,发现 982 个转录物在感染组织中差异表达(P < 0.05)。上调的转录物(699)主要与免疫反应功能相关,而下调的转录物(229)主要参与脂肪代谢。在 T = 192 h 时,所有上调的转录物都与组织愈合过程有关。比较三个大肠杆菌乳腺炎研究中在 T = 24 h 时检测到的 DE 基因,发现 248 个是共同的,主要涉及免疫反应功能。KEGG 途径分析表明,这些基因参与了 12 条与促炎反应和 APR 相关的途径,但也确定了两个意外途径的显著代表性:自然杀伤细胞介导的细胞毒性途径(KEGG04650)和 Rig-I 样受体信号通路(KEGG04622)。
在大肠杆菌引起的乳腺炎中,感染的乳腺组织显著上调与免疫反应相关的基因表达,并下调与脂肪代谢相关的基因。在 T = 24 h 时,三个大肠杆菌乳腺炎研究中共同的差异表达免疫反应基因中高达 25%独立于大肠杆菌菌株和剂量、奶牛泌乳阶段和数量、组织采集方法和基因分析方法。因此,这些 DE 基因可能代表乳腺中针对大肠杆菌的局部 APR 的重要介质。