Fasciola hepatica Infection in Cattle: Analyzing Responses of Peripheral Blood Mononuclear Cells (PBMC) Using a Transcriptomics Approach

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 log 2 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.

Identification of protective peptides of Fasciola hepatica-derived cathepsin L1 (FhCL1) in vaccinated sheep by a linear B-cell epitope mapping approach

“…This cell subset is not MHC restricted and can recognise peptides via a mechanism that requires direct cell-cell contact with an antigen presenting cell and signalling through the γδTC [45][46][47]. In addition, it was recently reported in two transcriptomic studies conducted in cattle and sheep infected with F. hepatica that major differences exist in the expressed genes related to immune response, and that the proportion of differentially expressed genes (DEGs) observed between acute and chronic stages of the infection was responsible for up to more than 70% of the total DEGs at the acute stage in sheep, whereas this percentage decreased to about 5% in cattle [48,49].…”

Insights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon

“…Regrettably, -omics studies aimed at investigating the changes in host tissues upon contact with FhNEJ are even more scarce than those focused on immature parasites. A few in vivo studies after F. hepatica infection have addressed transcriptomic analyses of peripheral blood mononuclear cells from sheep [92][93][94] and liver cells collected from sheep [95] and mice [96]. A novel proteomic analysis of the peritoneal fluid from infected sheep has also been recently published [97].…”

Transcriptomic Analysis of Ovine Hepatic Lymph Node Following Fasciola hepatica Infection – Inhibition of NK Cell and IgE-Mediated Signaling

“…On the other hand, differences in the immune response to infection may account for differences in host susceptibility. In the initial stages of infection there is a mixed systemic response with activation of T h 1/T h 2/Treg pathways, while in chronic infection the immune response shifts towards T h 2 activation, with sheep usually showing this pattern earlier than cattle (6)(7)(8). It has been shown that this shift is at least partly induced by molecules released by the parasite.…”