Mechanism of food allergy (FA) induction by medium chain triglycerides (MCT). (HYP7P.314)

Abstract

Food ingestion generally induces antigen (Ag)-specific tolerance rather than immunity. Consistent with this, induction of IgE-mediated intestinal FA in mice has required either Ag priming through a parenteral route or ingestion of Ag with a potent toxin. In contrast, we recently reported (JACI, 131:442-50, 2013) that Ag-specific, IgE-mediated FA is induced when a protein Ag is ingested with the widely used nutrient, MCT. We also showed that MCT ingestion induces increased epithelial cell expression of the pro-Th2 cytokines TSLP, IL-25 and IL-33. We now report that MCT ingestion, by itself, can induce shock by damaging intestinal epithelium, with a consequent increase in intestinal permeability. In contrast, ingestion of the anionic detergent, sodium dodecyl sulfate, damages intestinal epithelium but does not promote a Th2 response. Both direct MCT induction of intestinal epithelial damage and MCT promotion of a Th2 response and FA to co-ingested egg white are suppressed in mice treated with the lipase inhibitor orlistat, which blocks intestinal triglyceride absorption. Consistent with MCT induction of TSLP, IL-25 and IL-33, treatment with a cocktail of mAbs to these cytokines or their receptors blocks FA induction by ingested MCT plus egg white. Taken together, these observations suggest that MCT must be absorbed to damage epithelial cells and induce the pro-Th2 cytokines that promote FA development; they also provide a potential paradigm for natural FA development.