Transcriptional analysis identifies key genes involved in metabolism, fibrosis/tissue repair and the immune response against Fasciola hepatica in sheep liver

Background: Although fascioliasis has been relatively well studied, little is known about the molecular basis of this disease. This is particularly relevant, considering the very different response that sheep have to Fasciola hepatica relative to cattle. The acute phase of this disease is severe in sheep, whereas chronic fascioliasis is more common in cattle. Methods: To begin to explore the host-response to Fasciola in sheep and improve the understanding of the host-pathogen interactions during the parasite's migration through liver parenchyma to the bile duct, we used RNA sequencing (RNA-seq) to investigate livers from sheep infected for eight weeks compared with those from uninfected controls. Results: This study identified 572 and 42 genes that were up-and down-regulated, respectively, in infected livers relative to uninfected controls. Our molecular findings provide significant new insights into the mechanisms linked to metabolism, fibrosis and tissue-repair in sheep, and highlight the relative importance of specific components of immune response pathways, which appear to be driven toward a suppression of inflammation. Conclusions: This study is, to our knowledge, the first detailed investigation of the transcriptomic responses in the liver tissue of any host to F. hepatica infection. It defines the involvement of specific genes associated with the host's metabolism, immune response and tissue repair/regeneration, and highlights an apparent overlapping function of many genes involved in these processes.