A204 analysis and characterization of the excreted and secreted products of parasitic helminths as immunomodulators of inflammatory bowel disease

Abstract Background Parasitic helminths are known for their exceptional ability to modulate the host immune response in order to favour their survival. The excretory/secretory products (ESP), from Trichuris and Ascaris species are of keen interest for inflammatory bowel disease (IBD). Crohn’s disease and ulcerative colitis patients have benefitted from the administration of ova of T. suis in clinical trials, whereby symptoms were remediated through the ingestion of parasite ova, which subsequently hatch in the intestine. Our previous work has demonstrated the ability of T. suis ESP to downregulate secretion of inflammatory cytokines (TNF-α, IL-12) and increase the secretion of anti-inflammatory cytokines (IL-10) in murine bone marrow-derived macrophages. Aims This research aims to unveil the mechanisms of immune modulation by parasitic helminths in the context of IBD. We aim to characterize the cellular response in vitro, as well as the systemic response in vivo, in order to better characterize the scope of immune modulation that occurs with treatment. Methods Human peripheral blood mononuclear cell (PBMC) monocytes were purified and treated with helminth-derived products. The products were removed, and fresh media was added containing lipopolysaccharide (LPS) to stimulate cells. Supernatants were collected for cytokine analysis and cells were lysed and frozen. Mice were given 3% DSS or regular water for five days, and subsequently administered treatment with helminth-derived products, or a PBS control, once daily by intraperitoneal injection for 3–4 days. Weights were measured daily. On day 9 mice were sacrificed, colons lengths were measured, and spleens were collected for further analysis. Results We found that human PBMC monocytes treated with the ESP from T. suis and A. suum had decreased secretion of inflammatory cytokines (TNFα) and increased secretion of anti-inflammatory cytokines (IL-10). Additionally, we found that heminth products from A. suum had the ability to reverse the symptoms of weight loss and colon shrinking in DSS-mice compared to the control. Specifically, mice with DSS-induced colitis treated with metabolites increased their weight more than the PBS control (P < 0.0001) and had a longer colon compared to the PBS control (P < 0.001). Conclusions Taken together, these data generate an interest for intestinal helminth products as immunomodulators regarding treatment for patients suffering from inflammatory bowel disease (IBD). Funding Agencies NSERC and FRQNT