Abstract
As an adaption to their complex lifecycles, helminth parasites garner a unique repertoire of genes at different developmental stages with subtle regulatory mechanisms. These parasitic worms release differential components such as microRNAs (miRNAs) and extracellular vesicles (EVs) as mediators which participate in the host-parasite interaction, immune regulation/evasion, and in governing processes associated with host infection. MiRNAs are small (~ 22-nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level, and can exist in stable form in bodily fluids such as serum/plasma, urine, saliva and bile. In addition to reports focusing on the identification of miRNAs or in the probing of differentially expressed miRNA profiles in different development stages/sexes or in specific tissues, a number of studies have focused on the detection of helminth-derived miRNAs in the mammalian host circulatory system as diagnostic biomarkers. Extracellular vesicles (EVs), small membrane-surrounded structures secreted by a wide variety of cell types, contain rich cargos that are important in cell-cell communication. EVs have attracted wide attention due to their unique functional relevance in host-parasite interactions and for their potential value in translational applications such as biomarker discovery. In the current review, we discuss the status and potential of helminth parasite-derived circulating miRNAs and EV cargos as novel diagnostic tools.
Highlights
Parasitic helminths, comprising the Phylum Platyhelminthes and the Phylum Nematoda, are regarded as some of the most prevalent human infectious agents in developing countries (Hotez et al, 2008)
Small non-coding RNAs are a class of non-coding RNAs, which have been identified in a wide range of organisms including helminths (Cai et al, 2016). sncRNAs include housekeeping ncRNAs, such as small nuclear RNAs, transfer RNAs, and tRNAs-derived small RNAs; and regulatory ncRNAs, such as microRNAs, endogenous short interfering RNAs, and PIWI-interacting RNAs (Zhang et al, 2019)
With Echinococcus multilocularis, which causes the very serious alveolar echinococcosis (AE) in humans, deep sequencing showed that seven parasite-specific miRNAs were detectable in the sera of mice infected with this tapeworm; two of the miRNAs, emu-miR-10 and emu-miR-227, were amplified by RT-PCR, and may have potential as novel biomarkers for the diagnosis of AE (Guo and Zheng, 2017)
Summary
Parasitic helminths, comprising the Phylum Platyhelminthes and the Phylum Nematoda, are regarded as some of the most prevalent human infectious agents in developing countries (Hotez et al, 2008). Parasite-derived miRNAs (sma-miR-277, sma-miR-3479-3p and sma-bantam) were identified in the sera of S. mansoni-infected mice and patients from endemic areas in Zimbabwe and Uganda (Hoy et al, 2014) Detection of these miRNAs in human sera resulted in specificity/sensitivity values of 89%/80% and 80%/ 90%, respectively. With Echinococcus multilocularis, which causes the very serious alveolar echinococcosis (AE) in humans, deep sequencing showed that seven parasite-specific miRNAs were detectable in the sera of mice infected with this tapeworm; two of the miRNAs, emu-miR-10 and emu-miR-227, were amplified by RT-PCR, and may have potential as novel biomarkers for the diagnosis of AE (Guo and Zheng, 2017). Proteomics and RNAseq analysis of EVs from the rodent parasite Nippostrongylus brasiliensis, a model for human hookworm infection, identified 81 proteins, including 27 sperm-coating protein-like extracellular proteins in addition to those frequently found in exosomes (like tetraspanin, enolase, 14-3-3 protein, and heat shock proteins) and 52 miRNAs (Eichenberger et al, 2018a); these again warrant further study as potential diagnostic markers
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