In vitro investigation of the host-pathogen interaction in human strongyloidiasis at the intestinal level

Introduction Human strongyloidiasis is a chronic long-lasting infection caused by the helminth parasite Strongyloides stercoralis , characterised by a peculiar autoinfective cycle. The interplay between the parasite and the host should hence entail mechanisms of adaptation to tolerate the chronic presence of this nematode. However, the current knowledge of the mechanisms underpinning this interaction remains limited. To gain novel insights into the interaction between S. stercoralis and the human host, we employed multi-omics approaches to explore the modulation induced by S. stercoralis infective larvae (iL3) and their extracellular vesicles (EVs) on human intestinal epithelial cells. Methods S. stercoralis iL3 isolated from a clinical faecal sample were maintained in vitro for up to one week to allow the release of EVs in the conditioned medium. Human intestinal epithelial cells (Caco-2) were then exposed to either iL3 or their EVs for 6h, 24h or 72h. Results In our settings, different responses are triggered by the two iL3 or EVs over time. After 6 hours of coincubation, iL3 induced the release of pro-inflammatory cytokines, namely IL-8and CXCL10, while EVs only induced the release of CXCL10, with lower intensity compared to live larvae. Evaluation of gene expression modulation by transcriptomics and proteomics revealed that live larvae induced cellular activation and a pro-inflammatory like profile that peaked 72h post-exposure, while EVs displayed an earlier effect with modulation in mRNA and protein expression mostly 24h post-treatment and leading to a predominant inhibition of cell activation, metabolism and immune response. Discussion These findings highlight distinct effects mediated by iL3 and EVs in the local host-pathogen interaction during human strongyloidiasis. By showing a primary down-modulation of cell activation, we hypothesise that EVs may play a role in immune evasion. More in-depth investigations are needed to validate these findings and further elucidate the role of parasite-derived EVs in the pathophysiology of human strongyloidiasis.