Schistosoma excretory/secretory products: an untapped library of tolerogenic immunotherapeutics against food allergy

Food allergy (FA) is considered the ‘second wave’ of the allergy epidemic in developed countries after asthma and allergic rhinitis with a steadily growing burden of 40%. The absence of early childhood pathogen stimulation embodied by the hygiene hypothesis is one explanation, and in particular, the eradication of parasitic helminths could be at play. Infections with parasites Schistosoma spp. have been found to have a negative correlation with allergic diseases. Schistosomes induce regulatory responses to evade immune detection and ensure their long-term survival. This is achieved via excretory/secretory (E/S) products, consisting of proteins, lipids, metabolites, nucleic acids and extracellular vesicles, representing an untapped therapeutic avenue for the treatment of FA without the unpleasant side-effects and risks associated with live infection. Schistosome-derived immunotherapeutic development is in its infancy and novel discoveries are heavily technology dependent; thus, it is essential to better understand how newly identified molecules interact with host immune systems to ensure safety and successful translation. This review will outline the identified Schistosoma-derived E/S products at all life cycle stages and discuss known mechanisms of action and their ability to suppress FA.