title: The mycotoxin deoxynivalenol facilitates allergic sensitization to whey in mice.
abstract: Intestinal epithelial stress or damage may contribute to allergic sensitization against certain food antigens. Hence, the present study investigated whether impairment of intestinal barrier integrity by the mycotoxin deoxynivalenol (DON) contributes to the development of whey-induced food allergy in a murine model. C3H/HeOuJ mice, orally exposed to DON plus whey once a week for 5 consecutive weeks, showed whey-specific IgG1 and IgE in serum and an acute allergic skin response upon intradermal whey challenge, although early initiating mechanisms of sensitization in the intestine appeared to be different compared with the widely used mucosal adjuvant cholera toxin (CT). Notably, DON exposure modulated tight-junction mRNA and protein levels, and caused an early increase in IL-33, whereas CT exposure affected intestinal γδ T cells. On the other hand, both DON- and CT-sensitized mice induced a time-dependent increase in the soluble IL-33 receptor ST2 (IL-1R1) in serum, and enhanced local innate lymphoid cells type 2 cell numbers. Together, these results demonstrate that DON facilitates allergic sensitization to food proteins and that development of sensitization can be induced by different molecular mechanisms and local immune responses. Our data illustrate the possible contribution of food contaminants in allergic sensitization in humans.
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Bol-Schoenmakers
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Braber
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.|Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Akbari
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: de Graaff
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Roest
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Kruijssen
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Smit
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Nutricia Research, Utrecht, The Netherlands.
authors.forename: B C A M
authors.initials: BC
authors.lastname: van Esch
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Nutricia Research, Utrecht, The Netherlands.
authors.forename: P V
authors.initials: PV
authors.lastname: Jeurink
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Nutricia Research, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Garssen
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: R H H
authors.initials: RH
authors.lastname: Pieters
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002463:Cell Membrane Permeability; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007114:Immunization; D007365:Intercellular Junctions / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016269:Milk Hypersensitivity / Q000209:etiology*; D014255:Trichothecenes / Q000276:immunology*; D000067796:Whey / Q000276:immunology*
chemical_list: D000485:Allergens; D000906:Antibodies; D000067596:Interleukin-33; D014255:Trichothecenes; C007262:deoxynivalenol