The role of small RNA in parasite-host communication during Trichinella spiralis infection
The parasitic nematode Trichinella spiralis offers a bizarre and compelling example of host manipulation. Occupying both an enteric and intracellular muscle cell niche, the worm appears to hijack the host's innate cellular biological processes to bring about morphological shifts in the muscle cell which it inhabits, creating a more hospitable environment for the its own development. (1, 2). The molecular mechanisms underpinning this phenomenon are largely unknown. Recently there has been much
... terest in extracellular small RNAs secreted within exosomesextracellular vesicles, including in parasitic nematode infection (3). Here I investigate whether T. spiralis secretes small RNAs as part of its pathogenesis. I profiled small RNAs secreted by T. spiralis from both its adult (enteric) and muscle larval stages of the life cycle. My data suggest demonstrated that T. spiralis is indeed secretingsecretes miRNA (Chapters 3 and 4). Intriguingly the majority of small RNAs secreted by muscle stage larvae are not encapsulated within exosomesextracellular vesicles, consistent with its intracellular niche and implicating a novel secretory mechanism. Small RNAs enriched within the secreted fraction include those with homology to host miRNAs known to play a crucial role in muscle development and disease, such as miR-31 (Chapter 4). To test the role of secreted miRNAs in infection I generated an inducible expression system in the muscle cell line C2C12 (Chapter 5). Induction of exogenous miRNA expression and subsequent sequencing suggests that T. spiralis miR-31 is able to target host mRNA, with genes targeted including genes linked to muscular dystrophic disease (Chapter 6). I then describe further work which should be performed to solidify and expand upon the findings of this thesis (Chapter 7).