Allergic Sensitization to Whey in Mice Is Facilitated By the Mycotoxin Deoxynivalenol (DON)

Background: Orally ingested food proteins normally result in the induction of oral tolerance, whereas allergic sensitization to food proteins in mice is induced in the presence of a mucosal adjuvant like cholera toxin (CT). CT is therefore often used as a tool to unravel the mechanisms behind allergic sensitization, although CT is not involved in the onset of allergic sensitization in humans. The mycotoxin deoxynivalenol (DON) is among the most frequently detected contaminants of wheat and wheat-based products, and is able to impair intestinal barrier function. As such, we hypothesize that DON may represent a more human-relevant mucosal adjuvant and therefore the present study investigated the capacity of DON to act as a mucosal adjuvant in a mouse model of whey-induced food allergy. Methods: Female C3H/HeOuJ mice (n=8 per group) were orally exposed to DON plus whey once a week for 5 weeks, while control mice received DON in PBS. Acute allergic skin responses, change in body temperature and other anaphylactic shock reactions were measured upon whey-challenge. Allergen-specific antibodies and ST2 were measured in serum. mRNA expression of claudin-2 and -3, E-cadherin and IL-33 were determined in intestinal tissue and ST2 was measured in serum 6h after a single oral DON-exposure. Results: Mice exposed to DON plus whey showed whey-specific IgG1, IgG2a and IgE antibodies in serum and an acute allergic skin response upon intradermal whey challenge compared to control mice. Furthermore, a significant time-dependent increase in soluble ST2 in serum was observed in DON plus whey sensitized mice compared to control mice. In addition, analysis of intestinal tissues, isolated 6h after a single oral exposure to DON, revealed increased mRNA expression of the tight junction proteins claudin-2 and -3 and the adherens junction E-cadherin, as well as an increase in IL-33 mRNA accompanied by an increase in the soluble IL-33 receptor ST2 in serum. Conclusions: Together, these results demonstrate that DON facilitates allergic sensitization and may thus serve as a model adjuvant. Our data therefore illustrate the possible contribution of food contaminants, like DON, in allergic sensitization in humans.