Nitrated food proteins induce a regulatory immune response associated with allergy prevention after oral exposure in a Balb/c mouse food allergy model
Samadi N, Klems M, Heiden D, Bauer R, Kitzmüller C, Weidmann E, Ret D, Ondracek AS, Duschl A, Horejs-Hoeck J, Untersmayr E. Allergy. 2019 Aug 24. doi: 10.1111/all.14030. PMID: 31444907
Food allergy is associated with a high economic burden and a substantially reduced quality of life. As even to date a causative treatment is not commonly available, management of food allergy is primarily based on allergen avoidance. To modulate an ongoing allergic response towards tolerance, food compounds could be chemically modified. Protein nitration is a posttranslational phenomenon and diet derived nitrating agents might promote nitration in the gastrointestinal tract. Our group has previously investigated the impact of protein nitration on food allergy development. Oral administration of nitrated ovalbumin (OVA) under gastric acid suppression was not associated with sensitization. Moreover, exposing naïve mice to nitrated food protein resulted in an enhanced number of regulatory T cells (Tregs) as well as elevated IL-10 and IFN-γ levels.
Based on these previous findings, we studied the impact of pretreatment with nitrated food proteins on the immune response in a mouse food allergy model and on human monocyte-derived dendritic cells (moDCs) and peripheral blood mononuclear cells (PBMCs).
The model allergen OVA was nitrated in different nitration degrees (nitrated OVA (nitroOVA) and maximally nitrated OVA (nitroOVAmax)). NitroOVAmax pre-treated and subsequently sensitized mice showed reduced IgE, IgG1 and IgG2a antibody levels compared to the other groups. Moreover, Treg signals were significantly enhanced only in mice pre-treated with nitroOVAmax before sensitization. In moDCs, nitroOVAmax pre-treatment induced a regulatory DC phenotype by reduced expression of the activation marker CD86, while in and PBMCs enhanced IL-10 secretion and higher number of memory Tregs proliferation was observed.
Our data indicate that oral pretreatment with highly nitrated proteins induces a tolerogenic immune response in a food allergy mouse model and in human immune cells.