Molecular characterisation of extracellular vesicles released by Strongyloides stercoralis infective larvae isolated from a clinical sample
Extracellular vesicles (EVs) represent a key mechanism of host-pathogen crosstalk. Numerous helminth parasites have already been reported to shed EV-like structures carrying biomolecules with functional effects on target cells. However, the ability of Strongyloides. stercoralis to release EVs has yet to be demonstrated.  Following the isolation of S. stercoralis infective larvae (iL3s) form faecal samples obtained from a patient with strongyloidiasis, we showed that iL3s maintained in vitro for up to 48h release EVs-like structures. Transmission electron microscopy and nanoparticle tracking analysis highlighted vesicular structures enclosed by a bilayer and having a diameter of 120 nm in range. The further multi-omics characterisation of EV molecular cargo, revealed the presence of parasite-derived proteins and small RNAs (sRNAs), only partly shared with the somatic proteome or miRNome. EV molecular cargo encompassed proteins with enzymatic activities, immunogenic properties or already proposed as associated with Strongyloides spp. parasitism, thus potentially involved in the early stages of infection. Similarly, sRNAs, including microRNAs, conveyed by S. stercoralis iL3-EVs were predicted to target human genes associated with the regulation of gene expression and immune response. These findings highlight EVs shed by S. stercoralis iL3s as an additional tool for host-pathogen interaction. More in depth investigations of these EVs may provide additional insights into the pathophysiology of strongyloidiasis as well as novel targets for clinical applications.
Extracellular vesicles (EVs) represent a key mechanism of host-pathogen crosstalk. Numerous helminth parasites have already been reported to shed EV-like structures carrying biomolecules with functional effects on target cells. However, the ability of Strongyloides. stercoralis to release EVs has yet to be demonstrated.  Following the isolation of S. stercoralis infective larvae (iL3s) form faecal samples obtained from a patient with strongyloidiasis, we showed that iL3s maintained in vitro for up to 48h release EVs-like structures. Transmission electron microscopy and nanoparticle tracking analysis highlighted vesicular structures enclosed by a bilayer and having a diameter of 120 nm in range. The further multi-omics characterisation of EV molecular cargo, revealed the presence of parasite-derived proteins and small RNAs (sRNAs), only partly shared with the somatic proteome or miRNome. EV molecular cargo encompassed proteins with enzymatic activities, immunogenic properties or already proposed as associated with Strongyloides spp. parasitism, thus potentially involved in the early stages of infection. Similarly, sRNAs, including microRNAs, conveyed by S. stercoralis iL3-EVs were predicted to target human genes associated with the regulation of gene expression and immune response. These findings highlight EVs shed by S. stercoralis iL3s as an additional tool for host-pathogen interaction. More in depth investigations of these EVs may provide additional insights into the pathophysiology of strongyloidiasis as well as novel targets for clinical applications.
IRCCS Sacro Cuore Don Calabria Hospital