Transcriptomic Study on Ovine Immune Responses to <i>Fasciola hepatica</i> Infection

<div><p>Background</p><p><i>Fasciola hepatica</i> is not only responsible for major economic losses in livestock farming, but is also a major food-borne zoonotic agent, with 180 million people being at risk of infection worldwide. This parasite is sophisticated in manipulating the hosts’ immune system to benefit its own survival. A better understanding of the mechanisms underpinning this immunomodulation is crucial for the development of control strategies such as vaccines.</p><p>Methodology/principal findings</p><p>This <i>in vivo</i> study investigated the global gene expression changes of ovine peripheral blood mononuclear cells (PBMC) response to both acute & chronic infection of <i>F</i>. <i>hepatica</i>, and revealed 6490 and 2364 differential expressed genes (DEGS), respectively. Several transcriptional regulators were predicted to be significantly inhibited (e.g. <i>IL12</i> and <i>IL18</i>) or activated (e.g. <i>miR155-5p</i>) in PBMC during infection. Ingenuity Pathway Analysis highlighted a series of immune-associated pathways involved in the response to infection, including ‘Transforming Growth Factor Beta (TGFβ) signaling’, ‘Production of Nitric Oxide in Macrophages’, ‘Toll-like Receptor (TLRs) Signaling’, ‘Death Receptor Signaling’ and ‘<i>IL17</i> Signaling’. We hypothesize that activation of pathways relevant to fibrosis in ovine chronic infection, may differ from those seen in cattle. Potential mechanisms behind immunomodulation in <i>F</i>. <i>hepatica</i> infection are a discussed.</p><p>Significance</p><p>In conclusion, the present study performed global transcriptomic analysis of ovine PBMC, the primary innate/adaptive immune cells, in response to infection with <i>F</i>. <i>hepatica</i>, using deep-sequencing (RNAseq). This dataset provides novel information pertinent to understanding of the pathological processes in fasciolosis, as well as a base from which to further refine development of vaccines.</p>