"Excretory/secretory molecules released by the intestinal parasite Trichuris modulate the host immune response" Dr. Armando Jardim (McGill University)

The incidence of allergic and auto-immune disorders in industrialized countries has increased dramatically over the past century events that have been linked to “hygiene hypothesis”. This assumption is supported by growing evidence showing that helminths may play a protective role in shaping the host immunological response and inducing a balance between the Th1 and Th2 branches of the immune system. The pig whipworm Trichuris suis has become an interesting model to study this phenomenon. Many studies, in humans have clearly shown that T. suis suppresses clinical symptoms of several autoimmune diseases such as inflammatory bowel diseases (IBD), multiple sclerosis (MS), and possibly autism. In fact, T. suis ova are being clinically evaluated as a treatment for IBD. It is known that T. suis excreted/secreted (ES) molecules have immunomodulatory properties and are likely implicated in these immunotherapeutic events. To identify the immunoactive components, we performed proteomic analyses on ES collected in vitro from different life stages of the parasite. Tandem-mass spectrometry (MS/MS) analyses generated a list of ~300 proteins with temporal expression profiles. Treating immune cells in vitro inhibited stimuli-induced production of pro-inflammatory cytokines, namely IL-12 and TNF-alpha. More interestingly, these parasite ES alone induced expression of the anti-inflammatory cytokine IL-10. Finally, solid phase extractions of parasite conditioned culture media confirmed that small molecular weight metabolites released by the worms have immunomodulatory properties that could act concertedly with proteins to modulate host immune functions. A better understanding of how helminths affect the hosts' immune system may help pave the way to improved therapeutic strategy for autoimmune diseases.

Dr. Jardim is the guest of Prof. Ann English