C Britton1; A D Winter1; N D Marks1; H Y Gu1; K Maitland1; V Gillan1; E Devaney1;
1 Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, UK, UK
DiscussionThe mechanisms regulating development and survival of parasitic helminths within their hosts are not well understood. We are examining microRNAs in parasitic nematodes to investigate potential roles in development and immune modulation. microRNAs (miRNAs) are small (~22 nucleotide) non-coding RNAs that regulate gene expression at the post-transcriptional level. They are expressed in a diverse range of organisms from viruses to humans. We previously identified 192 miRNAs in the ovine gastrointestinal nematode Haemonchus contortus and, using microarray analysis, have begun to examine the functions of these. Two miRNAs are enriched in the infective L3 larval stage and genetic knockout of the homologous miRNAs in the free-living nematode Caenorhabditis elegans prevents arrest as dauer stage larvae, considered analogous to parasite infective L3. The two miRNAs are predicted to suppress metabolic processes associated with development and may act in parallel to the insulin-signaling pathway to regulate developmental progression. In contrast to the L3 stage, many novel miRNAs are upregulated in the L4 and adult stages of H. contortus. Using small RNA sequencing we have identified that some of these are present in excretory-secretory (ES) products and in extracellular vesicles (EVs) released from L4 and adult worms in vitro. Secreted miRNAs can also be detected in abomasal tissue from H. contortus infected sheep and we speculate that these may modulate immune outcome. Our results indicate that miRNAs play important roles in development and in host-parasite interactions and identify miRNAs and the pathways they regulate as potential targets of parasite control.