Extracellular Vesicle-Contained microRNA of C. elegans as a Tool to Decipher the Molecular Basis of Nematode Parasitism

Abstract

Among the fundamental biological processes affected by microRNAs, small regulators of gene expression, a potential role in host-parasite communication is intriguing. We compared the miRNA complement of extracellular vesicles released by the free-living nematode Caenorhabditis elegans in culture to that of other adult parasitic nematodes. Expecting convergent functional roles for secreted miRNAs due to the common parasitic lifestyle of the organisms under investigation, we performed a miRNA sequence analysis as well as target search and pathway enrichment for potential mRNA targets within host immune functions. We found that the parasite miRNA seed sequences were more often identical to those of C. elegans, rather than to those of their hosts. However, we observed that the nematode-secreted miRNA fractions shared more often seed sequences with host miRNAs than those that are not found in the extracellular environment. Development and proliferation of immune cells was predicted to be affected several-fold by nematode miRNA release. In addition, we identified the AGE-RAGE signaling as a convergent targeted pathway by species-specific miRNAs from several parasitic species. We propose a multi-species comparative approach to differentiate those miRNAs that may have critical functions in host modulation, from those that may not. With our simple analysis, we put forward a workflow to study traits of parasitism at the miRNA level. This work will find even more resonance and significance, as an increasing amount of parasite miRNA collections are expected to be produced in the future.

Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo

“…Our work establishes C. elegans as a discovery platform for animal EV biology. We obtained a much greater depth of C. elegans EV protein identification than in previous studies [72,73] via use of a mixed-stage C. elegans population with males and hermaphrodites, enrichment via buoyant density centrifugations, and direct visualization of GFP-labeled EV fractions of interest. The proteogenomic mining approach that we applied to EV cargo candidates lead to the discovery of four novel ciliary EV cargoes.…”

Nematode microRNAs can Individually Regulate Interferon Regulatory Factor 4 and mTOR in Differentiating T Helper 2 Lymphocytes and Modulate Cytokine Production in Macrophages

“…Secreted miRNA lists from H. polygyrus bakeri, T. muris, and A. suum were retrieved from the literature (Buck et al, 2014;Tritten et al, 2017;Eichenberger et al, 2018b;Hansen et al, 2019). Target prediction in the mouse genome for the top 20 most abundant miRNAs was performed as described previously (Duguet et al, 2020) using the TargetScan software package v. 7 (http://www. targetscan.org), implemented as a standalone workflow under iPortal (Kunszt et al, 2015) and openBIS (Bauch et al, 2011), using default parameters (Agarwal et al, 2015).…”

Revisiting the Schistosoma japonicum life cycle transcriptome for new insights into lung schistosomula development

“…The Reactome database incorporates a species comparison tool, enabling comparative analysis between human pathways and those predicted in the model organism Caenorhabditis elegans Stein, 2012, Fabregat, et al, 2018). Widely used for research in developmental biology, there is extensive knowledge of its biology and genome, C. elegans is very well characterised (Duguet, et al, 2020). Therefore, a comparison between the free-living nematode; C. elegans, and the parasitic platyhelminth S. japonicum can be used to reveal the molecular basis of parasitism.…”

“…Therefore, a comparison between the free-living nematode; C. elegans, and the parasitic platyhelminth S. japonicum can be used to reveal the molecular basis of parasitism. C. elegans and S. japonicum through releasing extracellular vehicles (EVs) may play a vital role in both organisms and aspects of their behaviour (de la Torre-Escudero, et al, 2019, Duguet, et al, 2020. In this context, using the model organism as a comparator was beneficial in terms of developmental biology and host-parasite interactions.…”