Abstract
BackgroundFasciola hepatica 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.Methodology/principal findingsThis in vivo study investigated the global gene expression changes of ovine peripheral blood mononuclear cells (PBMC) response to both acute & chronic infection of F. hepatica, and revealed 6490 and 2364 differential expressed genes (DEGS), respectively. Several transcriptional regulators were predicted to be significantly inhibited (e.g. IL12 and IL18) or activated (e.g. miR155-5p) 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 ‘IL17 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 F. hepatica infection are a discussed.SignificanceIn conclusion, the present study performed global transcriptomic analysis of ovine PBMC, the primary innate/adaptive immune cells, in response to infection with F. hepatica, 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.
Highlights
The trematode parasite Fasciola hepatica is the causative agent of a global disease that is of major health, welfare and economic importance in domestic animals [1]
In this study we investigated global gene expression changes of the primary innate/adaptive immunity-related cells from sheep pre- and post- infected with F. hepatica, which revealed the underpinning mechanisms behind various aspects of fluke-induced immunomodulation, including fibrosis, nitric oxide production, regulation of Toll-like receptors, apoptosis of immune cells, and Th17 differentiation
We hypothesis that activation of pathways relevant to fibrosis in ovine chronic infection, may differ from those seen in cattle
Summary
The trematode parasite Fasciola hepatica (liver fluke) is the causative agent of a global disease (fasciolosis) that is of major health, welfare and economic importance in domestic animals (cattle, sheep) [1]. This parasite can infect and complete its lifecycle in a wide range of other mammals including humans [2]. Fasciola hepatica is responsible for major economic losses in livestock farming, but is 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
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