Oral Presentation International Veterinary Immunology Symposium 2016

Transcriptomic profile of liver and PBMCs in sheep - induction of immune-related genes in response to Fasciola hepatica (#13)

Cristian Alvarez 1 , Brendan R Ansell 1 , Ross S Hall 1 , Robin B Gasser 1 , Aaron R Jex 2 , Jean-Pierre Y Scheerlinck 1
  1. The University of Melbourne, Melbourne/Parkville, VIC, Australia
  2. Population Health and Immunity, Walter and Eliza Hall Institute, Melbourne, VIC, Australia

Fasciola hepatica is responsible for fascioliasis in livestock and humans, causing extensive liver damage and chronic inflammation of the bile ducts. In sheep, the acute phase is particularly severe and parasites are thought to bias immunity towards Th2 responses.

Using RNA sequencing (RNA-seq) we investigate the transcriptome of livers and peripheral blood mononuclear cells (PBMCs) from sheep infected with F. hepatica and compared these responses with those from uninfected controls. In infected livers, 572 genes were up regulated, while 42 were down regulated relative to uninfected controls. Unsurprisingly considering the extensive liver damage from migratory Fasciola larvae, increased gene expression was associated with fibrosis and tissue-repair in infected livers. Interestingly, concurrent with tissue repair, gene expression profiles also suggested a tendency toward a suppression of inflammation in the livers of infected sheep. We also characterized transcriptomic changes in peripheral blood mononuclear cells (PBMCs) collected from sheep at three time points over the first eight weeks of infection relative to contemporary, uninfected controls. In total, 183 and 76 genes were found to be differentially transcribed at two and eight weeks post-infection respectively. Functional and pathway analysis of differentially transcribed genes revealed changes related to T-cell activation that may underpin a Th2-biased immune response against this parasite.

In conclusions, this study defines specific genes associated with the host’s metabolism, tissue repair/regeneration and immune response that are regulated during F hepatica infection, and highlights overlapping functions of many genes involved.