Abstract
The parasitic helminth Fasciola hepatica (liver fluke) causes economic loss to the livestock industry globally and also causes zoonotic disease. New control strategies such as vaccines are urgently needed, due to the rise of drug resistance in parasite populations. Vaccine development requires a comprehensive understanding of the immunological events during infection. Previous in vivo studies by our group have investigated global differentially expressed genes (DEGs) in ovine peripheral blood mononuclear cells (PBMC) in response to both acute and chronic F. hepatica infection. This work demonstrated that pathways involved in the pathogenesis of ovine fasciolosis included fibrosis, inhibition of macrophage nitric oxide production, and antibody isotype switching, among others. Transcriptomic changes in PBMC populations following F. hepatica infection in cattle, in which the disease phenotype is quite different, have not yet been examined. Using RNA sequencing we investigated gene expression changes in PBMC isolated from 9 non-infected and 11 F. hepatica-experimentally-infected calves immediately before infection, at 1 and at 14 weeks post-infection. Longitudinal time-course comparisons between groups revealed 21 and 1,624 DEGs driven exclusively by F. hepatica infection in cattle at acute and chronic stages, respectively. These results show that fewer DEGs at the acute stage of infection can be identified in cattle, as compared with sheep. In addition, the log2 fold-changes of these DEGs were relatively low (−1 to 3) reflecting the different clinical presentation of F. hepatica infection in cattle. Gene pathways for hepatic fibrosis and hepatic cholestasis along with apoptosis of antigen-presenting cells were enriched at chronic stages. Our results reflect the major differences in the disease phenotype between cattle and sheep and may indicate pathways to target in vaccine development.
Highlights
The liver flukes Fasciola hepatica and Fasciola gigantica are parasitic trematodes that affect cattle, sheep and goats, worldwide causing significant economic loses to agriculture [1, 2]
Baermann tests were negative for all animals at week 0 (W0) and W14 ruling out the presence of lungworm infection during the experimental period
We suggest that the “fibrosis of liver” downstream effect could have been initiated at the chronic stage by the upregulation of tumor necrosis factor gene (TNF) and that TGFB1 would contribute to the fibrotic effect at more advanced stages
Summary
The liver flukes Fasciola hepatica and Fasciola gigantica are parasitic trematodes that affect cattle, sheep and goats, worldwide causing significant economic loses to agriculture [1, 2]. Several research projects are pursuing alternative prophylactic and therapeutic strategies including new active compounds [9] and vaccines [10] The latter are especially desirable as vaccines could reduce the use of flukicides, slowing the emergence of anthelmintic resistance in the future, and do not leave drug residues that present risks both to the environment and to consumers of animal products
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