On the presence and immunoregulatory functions of extracellular microRNAs in the trematode Fasciola hepatica

Abstract

Liver flukes represent a paraphyletic group of endoparasitic flatworms that significantly affect man either indirectly due to economic damage on livestock or directly as pathogens. A range of studies have focussed on how these macroscopic organisms can evade the immune system and live inside a hostile environment such as the mammalian liver and bile ducts. Recently, microRNAs, a class of short noncoding gene regulators, have been proposed as likely candidates to play roles in this scenario. MicroRNAs (miRNAs) are key players in development and pathogenicity and are highly conserved between metazoans: identical miRNAs can be found in flatworms and mammalians. Interestingly, miRNAs are enriched in extracellular vesicles (EVs) which are secreted by most cells. EVs constitute an important mode of parasite/host interaction, and recent data illustrate that miRNAs play a vital part. We have demonstrated the presence of miRNAs in the EVs of the trematode species Dicrocoelium dendriticum and Fasciola hepatica (Fhe) and identified potential immune-regulatory miRNAs with targets in the host. After our initial identification of miRNAs expressed by F. hepatica, an assembled genome and additional miRNA data became available. This has enabled us to update the known complement of miRNAs in EVs and speculate on potential immune-regulatory functions that we review here.

The secretome of a parasite alters its host’s behaviour but does not recapitulate the behavioural response to infection

“…Such a link has almost never been established in previous studies of parasitic manipulation (9). Parasites release a wide variety of molecules into their external environment, including lipids (10), nucleic acids (11) and proteins (12), which are sometimes included in extracellular vesicles (13). These molecules are collectively referred to as the secretome.…”

miRNAgFree: prediction and profiling of novel microRNAs without genome assembly

“…the top 14 guide sequences in mouse and the top 44 in zebrafish are all correct (see column c in Table 1). Finally, using publically available data for F. hepatica (SRR1825354) we detected a member of the let-7 family which was not reported in the most recent complement using the genome assembly (Fromm et al, 2017) either due to assembly quality or structural properties which prevented its prediction (see supplementary figure 1). b is the applied duplex bindings threshold, N the total number of predicted miRNAs, p is the proportion of correct guide sequences (annotated in miRBase 21), p25 is the same as p but just considering the top quartile of predictions, c is the number of consecutive correct predictions among the top expressed ones.…”

Evolutionary implications of the microRNA- and piRNA complement of Lepidodermella squamata (Gastrotricha)

“…Interestingly, we found seven miRNAs of conserved families with particularly long hairpins (Let-7, Mir-750, Mir-22, Mir-31, Mir-1992, Mir-1) that exceeded commonly observed hairpin-sizes of 60-90 nucleotides (nt) with miRNA precursor lengths up to 386 nucleotides (Mir-750) (Figure 1b and 1c). Such long precursors are so far only described in flatworms [39,[48][49][50] .…”