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Hypothesis and Theory ARTICLE

Front. Immunol. | doi: 10.3389/fimmu.2020.608686

An evaluation of the Fasciola hepatica miRnome predicts a targeted regulation of mammalian innate immune responses Provisionally accepted The final, formatted version of the article will be published soon. Notify me

  • 1Faculty of Science, University of Technology Sydney, Australia
  • 2University of Technology Sydney, Australia

Understanding mechanisms by which parasitic worms (helminths) control their hosts’ immune responses is critical to the development of effective new disease interventions. Fasciola hepatica, a global scourge of humans and their livestock, suppresses host innate immune responses within hours of infection, ensuring that host protective responses are quickly incapacitated. This allows the parasite to freely migrate from the intestine, through the liver to ultimately reside in the bile duct, where the parasite establishes a chronic infection that is largely tolerated by the host. The recent identification of micro(mi)RNA, small RNAs that regulate gene expression, within the extracellular vesicles secreted by helminths suggest that these non-coding RNAs may have a role in the parasite-host interplay. To date 77 miRNAs have been identified in F. hepatica comprising primarily of ancient conserved species of miRNAs. We hypothesised that many of these miRNAs are utilised by the parasite to regulate host immune signalling pathways. To test this theory, we first compiled all of the known published F. hepatica miRNAs and critically curated their sequences and annotations. Then with a focus on the miRNAs expressed by the juvenile worms, we predicted gene targets within human innate immune cells. This approach revealed the existence of targets within every immune cell, providing evidence for the universal management of host immunology by this parasite. Notably, there was a high degree of redundancy in the potential for the parasite to regulate the activation of dendritic cells, eosinophils and neutrophils, with multiple miRNAs predicted to act on singular gene targets within these cells. This original exploration of the Fasciola miRnome offers the first molecular insight into mechanisms by which F. hepatica can regulate the host protective immune response.

Keywords: Fasciola, helminth, miRNA, Immune Modulation, dendritic cell, eosinophil, Neutrophil

Received: 21 Sep 2020; Accepted: 09 Dec 2020.

Copyright: © 2020 Ricafrente, Nguyen, Tran and Donnelly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sheila Donnelly, University of Technology Sydney, Sydney, 2007, New South Wales, Australia, Sheila.Donnelly@uts.edu.au