Abstract
Fasciola spp. liver flukes have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile Fasciola hepatica facilitate control target validation in the most pathogenic life stage. Comparative transcriptomics of in vitro and in vivo maintained 21 day old F. hepatica finds that 86% of genes are expressed at similar levels across maintenance treatments suggesting commonality in core biological functioning within these juveniles. Phenotypic comparisons revealed higher cell proliferation and growth rates in the in vivo juveniles compared to their in vitro counterparts. These phenotypic differences were consistent with the upregulation of neoblast-like stem cell and cell-cycle associated genes in in vivo maintained worms. The more rapid growth/development of in vivo juveniles was further evidenced by a switch in cathepsin protease expression profiles, dominated by cathepsin B in in vitro juveniles and by cathepsin L in in vivo juveniles. Coincident with more rapid growth/development was the marked downregulation of both classical and peptidergic neuronal signalling components in in vivo maintained juveniles, supporting a role for the nervous system in regulating liver fluke growth and development. Differences in the miRNA complements of in vivo and in vitro juveniles identified 31 differentially expressed miRNAs, including fhe-let-7a-5p, fhe-mir-124-3p and miRNAs predicted to target Wnt-signalling, which supports a key role for miRNAs in driving the growth/developmental differences in the in vitro and in vivo maintained juvenile liver fluke. Widespread differences in the expression of neuronal genes in juvenile fluke grown in vitro and in vivo expose significant interplay between neuronal signalling and the rate of growth/development, encouraging consideration of neuronal targets in efforts to dysregulate growth/development for parasite control.
Funder
National Centre for the Replacement, Refinement and Reduction of Animals in Research
Biotechnology and Biological Sciences Research Council
Department for Education, UK Government
Department of Agriculture, Environment and Rural Affairs, UK Government
Publisher
Public Library of Science (PLoS)
Subject
Infectious Diseases,Public Health, Environmental and Occupational Health
Reference103 articles.
1. The “Neglected” Neglected Worms;World Health Organisation;Action Against Worms,2007
2. Recent developments in the epidemiology, diagnosis, and treatment of Fasciola infection;C Webb;Current Opinion in Infectious Diseases,2018
3. Drug resistance in liver flukes. International Journal for Parasitology;I Fairweather;Drugs and Drug Resistance,2020
4. Fascioliasis due to Fasciola hepatica and Fasciola gigantica infection: an update on this ‘neglected’ neglected tropical disease;RW Tolan;Laboratory Medicine,2011
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