Infection with the zoonotic trematode Fasciola hepatica, common in many regions with a temperate climate, leads to delayed growth and loss of productivity in cattle, while infection in sheep can have more severe effects, potentially leading to death. Previous transcriptomic analyses revealed upregulation of TGFB1, cell death and Toll-like receptor signalling, T-cell activation, and inhibition of nitric oxide production in macrophages in response to infection. However, the differences between ovine and bovine responses have not yet been explored. The objective of this study was to further investigate the transcriptomic response of ovine peripheral blood mononuclear cells (PBMC) to F. hepatica infection, and to elucidate the differences between ovine and bovine PBMC responses. Sixteen male Merino sheep were randomly assigned to infected or control groups (n = 8 per group) and orally infected with 120 F. hepatica metacercariae. Transcriptomic data was generated from PBMC at 0, 2 and 16 weeks post-infection (wpi), and analysed for differentially expressed (DE) genes between infected and control animals at each time point (analysis 1), and for each group relative to time 0 (analysis 2). Analysis 2 was then compared to a similar study performed previously on bovine PBMC. A total of 453 DE genes were found at 2 wpi, and 2 DE genes at 16 wpi (FDR < 0.1, analysis 1). Significantly overrepresented biological pathways at 2 wpi included role of PKR in interferon induction and anti-viral response, death receptor signalling and RIG-I-like receptor signalling, which suggested that an activation of innate response to intracellular nucleic acids and inhibition of cellular apoptosis were taking place. Comparison of analysis 2 with the previous bovine transcriptomic study revealed that anti-inflammatory response pathways which were significantly overrepresented in the acute phase in cattle, including IL-10 signalling, Th2 pathway, and Th1 and Th2 activation were upregulated only in the chronic phase in sheep. We propose that the earlier activation of anti-inflammatory responses in cattle, as compared with sheep, may be related to the general absence of acute clinical signs in cattle. These findings offer scope for “smart vaccination” strategies for this important livestock parasite.

感染人畜共患吸虫 肝片形吸虫，在许多温带气候地区很常见，导致牛的生长延迟和生产力下降，而绵羊的感染可能会产生更严重的影响，可能导致死亡。先前的转录组学分析揭示了TGFB1、细胞死亡和 Toll 样受体信号转导、T 细胞活化以及巨噬细胞响应感染时抑制一氧化氮产生。然而，尚未探索绵羊和牛反应之间的差异。本研究的目的是进一步研究绵羊外周血单个核细胞 (PBMC) 对肝吸虫感染，并阐明绵羊和牛 PBMC 反应之间的差异。16 只雄性美利奴绵羊被随机分配到感染组或对照组（每组 n = 8）并口服感染 120 F. 肝囊蚴。在感染后 (wpi) 0、2 和 16 周从 PBMC 生成转录组数据，并分析每个时间点（分析 1）和每组相对于时间的感染动物和对照动物之间的差异表达（DE）基因0（分析 2）。然后将分析 2 与之前对牛 PBMC 进行的类似研究进行比较。在感染后第 2 周发现了总共 453 个 DE 基因，在感染后第 16 周发现了 2 个 DE 基因（FDR < 0.1，分析 1）。包括 2 wpi 时显着过度表达的生物途径PKR 在干扰素诱导和抗病毒反应中的作用, 死亡受体信号 和 RIG-I 样受体信号转导，这表明对细胞内核酸的先天反应的激活和细胞凋亡的抑制正在发生。分析 2 与之前的牛转录组学研究的比较表明，在牛的急性期显着过度表达的抗炎反应通路，包括IL-10 信号, Th2通路， 和 Th1 和 Th2 激活仅在绵羊的慢性期上调。我们提出，与绵羊相比，牛更早激活抗炎反应可能与牛普遍没有急性临床症状有关。这些发现为这种重要的牲畜寄生虫提供了“智能疫苗接种”策略的空间。