Understanding liver fluke microRNA secretion – can small RNAs address a big problem with fluke control?

The liver fluke, Fasciola hepatica, is a global burden on the wellbeing and productivity of farmed ruminants, and a zoonotic threat to human health. It is widely accepted that improved understanding of fundamental parasite biology can identify targets for new anthelmintics. One promising area that remains underexplored is the molecular host-parasite interface, where the fundamental mechanisms used by flukes to survive within their hosts remain poorly understood. We know that fluke secrete micro (mi)RNAs, which could be key mediators of host interactions; data from other systems suggests that these could be interfered with for flukicidal effect. Our team has bolstered understanding of fluke miRNAs by expanding the F. hepatica miRNome to 150 mature sequences, including new species-specific miRNAs expressed across multiple life stages. These miRNAs are differentially expressed across metacercariae, juvenile and adult parasites and adult-derived extracellular vesicles (EVs). The majority of miRNAs were expressed most highly in metacercariae, with at least six distinct expression clusters apparent across life stages. Regarding host interactions, a subset of 28 miRNAs were detected in EVs, indicating their potential for delivery into host cells. We used in silico analysis to link these with downregulation of 397 host genes in published lymph node, peripheral blood mononuclear cell (PBMC) and liver tissues of animals carrying F. hepatica infections. Downregulated transcripts were involved in signal transduction, immune and metabolic pathways, suggesting that fluke-derived miRNAs could modulate the host environment during fasciolosis. We suggest that these data provide a set of potential targets for new control approaches based around miRNA inhibition, interfering with the parasite’s ability to invade and survive within the host animal.