Fang Lingzhao, Hou Yali, An Jing, Li Bingjie, Song Minyan, Wang Xiao, Sørensen Peter, Dong Yichun, Liu Chao, Wang Yachun, Zhu Huabin, Zhang Shengli, Yu Ying
Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural UniversityBeijing, China; Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus UniversityTjele, Denmark.
Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences Beijing, China.
Front Cell Infect Microbiol. 2016 Dec 26;6:193. doi: 10.3389/fcimb.2016.00193. eCollection 2016.
() is problematic for lactating mammals and public health. Understanding of mechanisms by which the hosts respond to severe invasion of remains elusive. In this study, the genome-wide expression of mRNAs and miRNAs in bovine mammary gland cells were interrogated at 24 h after intra-mammary infection (IMI) with high or low concentrations of . Compared to the negative control quarters, 194 highly-confident responsive genes were identified in the quarters with high concentration (10 cfu/mL) of , which were predominantly implicated in pathways and biological processes pertaining to innate immune system, such as cytokine-cytokine receptor interaction and inflammatory response. In contrast, only 21 highly-confident genes were significantly differentially expressed in face of low concentration (10 cfu/mL) of , which slightly perturbed the cell signaling and invoked corresponding responses like vasoconstriction, indicating limited perturbations and immunological evading. Additionally, the significant up-regulations of bta-mir-223 and bta-mir-21-3p were observed in the quarters infected by high concentration of . Network analysis suggested that the two miRNAs' pivotal roles in defending hosts against bacterial infection probably through inhibiting and . The significant down-regulation of was also observed in bovine mammary epithelial cells at 24 h post-infection of (10 cfu/mL) . Integrated analysis with QTL database further suggested 28 genes (e.g., , and ) as candidates of bovine mastitis. This study first systematically revealed transcriptional and post-transcriptional responses of bovine mammary gland cells to invading in a dosage-dependent pattern, and highlighted a complicated responsive mechanism in a network of miRNA-gene-pathway interplay.
()对哺乳期哺乳动物和公共卫生存在问题。宿主对严重入侵的反应机制仍不清楚。在本研究中,在乳腺内感染(IMI)高浓度或低浓度的 24 小时后,对牛乳腺细胞中 mRNA 和 miRNA 的全基因组表达进行了检测。与阴性对照乳腺相比,在高浓度(10 cfu/mL)的 乳腺中鉴定出 194 个高度可靠的反应基因,这些基因主要涉及与先天免疫系统相关的途径和生物学过程,如细胞因子 - 细胞因子受体相互作用和炎症反应。相比之下,面对低浓度(10 cfu/mL)的 ,只有 21 个高度可靠的基因有显著差异表达,这轻微扰乱了细胞信号传导并引发了如血管收缩等相应反应,表明干扰有限且具有免疫逃避作用。此外,在高浓度 感染的乳腺中观察到 bta - mir - 223 和 bta - mir - 21 - 3p 的显著上调。网络分析表明,这两种 miRNA 在保护宿主抵抗细菌感染中可能起关键作用,可能是通过抑制 和 。在感染 (10 cfu/mL)24 小时后的牛乳腺上皮细胞中也观察到 的显著下调。与 QTL 数据库的综合分析进一步表明 28 个基因(如 、 和 )是牛乳腺炎的候选基因。本研究首次系统地揭示了牛乳腺细胞对入侵 的转录和转录后反应呈剂量依赖性模式,并突出了 miRNA - 基因 - 途径相互作用网络中的复杂反应机制。