Deciphering the molecular mechanisms of helminth-host interactions
- Publication Type:
- Thesis
- Issue Date:
- 2025
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Parasitic worms (helminths) infect more than 1.5 billion people worldwide and cause major economic losses to the agricultural industry through infection of livestock. Their persistence is driven by their ability to modulate host immune responses, while current control strategies are increasingly limited by drug resistance, lack of vaccines, and poor diagnostics. This thesis investigated the role of parasite-derived microRNAs (miRNAs) in host-parasite interactions using Fasciola hepatica (liver fluke) as a model organism. The study identified distinct host- and parasite-derived circulating miRNA signatures associated with different stages of infection, demonstrating their potential as sensitive, stage-specific biomarkers for early diagnosis of fasciolosis. Importantly, this thesis revealed for the first time that parasite-derived miRNAs transferred to host cells are present as sequence length variants, known as isomiRs. The study demonstrated that these isomiRs can regulate mammalian immune cells and suggests that they are selectively deployed by the parasite to fine-tune host immune responses. The research also showed that these parasite-derived isomiRs remain functional even when key components of the host RNA interference pathway, Ago2 and Dicer, are disrupted, suggesting adaptation of flexible mechanisms to utilise mammalian RNAi pathways. Together, these findings provide new insights into helminth biology, advance understanding of cross-kingdom miRNA-mediated parasite-host communication and support the development of improved diagnostic and therapeutic strategies.
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