The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Genes (Basel). 2019 Aug 28;10(9):656. doi: 10.3390/genes10090656.
is a critical bovine pathogen, but its pathogenesis remains poorly understood. Here, the virulent HB0801 (P1) and attenuated HB0801-P150 (P150) strains of . were used to explore the potential pathogenesis and effect of induced immunity from calves' differential transcriptomes post infection. Nine one-month-old male calves were infected with P1, P150, or mock-infected with medium and euthanized at 60 days post-infection. Calves in P1 group exhibited other clinical signs and pathological changes compared to the other two groups. Transcriptome profiles of peripheral blood mononuclear cells revealed seven and 10 hub differentially expressed genes (DEGs) in P1 and P150 groups compared with mock-infected group, respectively. Then, P1-induced pathogenesis was predicted to be associated with enhanced Th17, and P150-induced immunity with Th1 response and expression of ubiquitination-associated enzymes. Association analysis showed that 14 and 11 DEGs were positively and negatively correlated with pathological changes, respectively. Furthermore, up-regulated expression in molecules critical to differentiation of pathogenic Th17 cells in lung and peripheral blood mononuclear cells in P1 group was validated at RNA and protein levels. The results confirmed virulent and attenuated strains might be associated with biased differentiation of pro-inflammatory pathogenic Th17 and Th1 subsets respectively.
是一种重要的牛病原体,但它的发病机制仍不清楚。本研究中,使用了毒力较强的 HB0801(P1)和毒力减弱的 HB0801-P150(P150)菌株,来探索感染后犊牛差异转录组中潜在的发病机制和诱导免疫的作用。将 9 头 1 月龄雄性犊牛分别用 P1、P150 或培养基进行感染,并在感染后 60 天安乐死。与其他两组相比,P1 组的犊牛表现出其他临床症状和病理变化。外周血单核细胞的转录组谱显示,与 mock 感染组相比,P1 和 P150 组分别有 7 个和 10 个差异表达基因(DEGs)。然后,预测 P1 诱导的发病机制与增强的 Th17 有关,而 P150 诱导的免疫与 Th1 反应和泛素化相关酶的表达有关。关联分析表明,14 个和 11 个 DEG 分别与病理变化呈正相关和负相关。此外,在 P1 组的肺和外周血单核细胞中,与致病性 Th17 细胞分化相关的关键分子的上调表达在 RNA 和蛋白水平上得到了验证。研究结果证实,强毒株和弱毒株可能分别与促炎致病性 Th17 和 Th1 亚群的偏分化有关。