Timing of Transcriptomic Peripheral Blood Mononuclear Cell Responses of Sheep to Fasciola hepatica Infection Differs From Those of Cattle, Reflecting Different Disease Phenotypes

Abstract

Infection with the zoonotic trematode Fasciola hepatica, common in many regions with a temperate climate, leads to delayed growth and loss of productivity in cattle, while infection in sheep can have more severe effects, potentially leading to death. Previous transcriptomic analyses revealed upregulation of TGFB1, cell death and Toll-like receptor signalling, T-cell activation, and inhibition of nitric oxide production in macrophages in response to infection. However, the differences between ovine and bovine responses have not yet been explored. The objective of this study was to further investigate the transcriptomic response of ovine peripheral blood mononuclear cells (PBMC) to F. hepatica infection, and to elucidate the differences between ovine and bovine PBMC responses. Sixteen male Merino sheep were randomly assigned to infected or control groups (n = 8 per group) and orally infected with 120 F. hepatica metacercariae. Transcriptomic data was generated from PBMC at 0, 2 and 16 weeks post-infection (wpi), and analysed for differentially expressed (DE) genes between infected and control animals at each time point (analysis 1), and for each group relative to time 0 (analysis 2). Analysis 2 was then compared to a similar study performed previously on bovine PBMC. A total of 453 DE genes were found at 2 wpi, and 2 DE genes at 16 wpi (FDR < 0.1, analysis 1). Significantly overrepresented biological pathways at 2 wpi included role of PKR in interferon induction and anti-viral response, death receptor signalling and RIG-I-like receptor signalling, which suggested that an activation of innate response to intracellular nucleic acids and inhibition of cellular apoptosis were taking place. Comparison of analysis 2 with the previous bovine transcriptomic study revealed that anti-inflammatory response pathways which were significantly overrepresented in the acute phase in cattle, including IL-10 signalling, Th2 pathway, and Th1 and Th2 activation were upregulated only in the chronic phase in sheep. We propose that the earlier activation of anti-inflammatory responses in cattle, as compared with sheep, may be related to the general absence of acute clinical signs in cattle. These findings offer scope for “smart vaccination” strategies for this important livestock parasite.

Evaluation of Th1/Th2, regulatory cytokines and transcriptional factor FoxP3 in sheep immunized with a partially protective and non-protective vaccine and challenged with Fasciola hepatica

“…The similar gene expression for IL-10 in the liver of UC and IC groups in the present study agreed with the expression of this cytokine in the liver of sheep chronically infected with F. hepatica [ 22 ], but it contrasted with the higher levels of IL-10 expression in the livers of buffaloes infected with F. gigantica [ 27 ], suggesting that the different expression of this cytokine may be due either to the different host species which has been described previously in PBMC of sheep and cattle infected with F. hepatica [ 35 ] or parasite species. In the livers of sheep during acute stages of F. hepatica infection (9 and 18 dpi), a marked increase of IL-10 gene expression was recorded in infected and vaccinated groups with respect to the uninfected control group [ 9 ] which suggests a different expression pattern of IL-10 during the migratory and biliary stages of the infection.…”

Genome-Wide Association Study for Haemonchus contortus Resistance in Morada Nova Sheep

“…TREML1 (or TLT-1), TREM2, and TREM1 genes, which are involved in inflammatory, innate, and adaptive immune responses, were associated with tick resistance in cattle [31], and the role of TRML1 in clot formation and inflammatory or immune-induced bleeding has been reported [32,33]. Furthermore, increased expression of TREM1 was detected in sheep peripheral blood mononuclear cells during chronic infection with Fasciola hepatica [34]. FER, a tyrosine kinase involved in leukocyte recruitment, regulated the intestinal epithelial lipopolysaccharide barrier in response to bacteria [35].…”

Transcriptomic meta-analysis reveals unannotated long non-coding RNAs related to the immune response in sheep

“…These genes were part of the iFMDV-associated co-expression module and many were also part of the DCN. The IFN response was mostly driven by the inactivated vaccine ( Braun et al, 2018 ; Jouneau et al, 2020 ) and the LPS stimulation datasets ( Bush et al, 2020 ), while the helminth infection ( Fu et al, 2016 ; Niedziela et al, 2021 ) and other smaller datasets ( Varela-Martínez et al, 2018 ; Wang et al, 2019 ; Guo et al, 2020 ) produced a different expression profile, as seen in the stimulation-correlated co-expression modules. In the same manner as known ISGs, lncRNAs can also be induced by IFN and have important roles in controlling pathogen infection and resolution of the immune response, or they can regulate the IFN mediated host defence ( Meng et al, 2017 ; Qiu et al, 2018 ).…”