Nitrated food proteins induce a regulatory immune response associated with allergy prevention after oral exposure in a Balb/c mouse food allergy model. Issue 2 (1st October 2019)

• Record Type: Journal Article
• Authors: Samadi, Nazanin; Klems, Martina; Heiden, Denise; Bauer, Renate; Kitzmüller, Claudia; Weidmann, Eleonore; Ret, Davide; Ondracek, Anna S.; Duschl, Albert; Horejs‐Hoeck, Jutta; Untersmayr, Eva
• Is Part Of: Allergy. Volume 75:Issue 2(2020)
• Page Start: 412
• Page End: 422
• Publication Date: 2019-10-01
• Subjects: allergy prevention -- food allergy -- immune modulation -- protein nitration -- regulatory T cells; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.14030
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: Food allergy is associated with a high personal health and economic burden. For immunomodulation toward tolerance, food compounds could be chemically modified, for example, by posttranslational protein nitration, which also occurs via diet‐derived nitrating agents in the gastrointestinal tract. Objective: We sought to analyze the effect 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 PBMCs. Methods: The model allergen ovalbumin (OVA) was nitrated in different nitration degrees, and the secondary structures of proteins were determined by circular dichroism (CD). Allergy‐preventive treatment with OVA, nitrated OVA (nOVA), and maximally nitrated OVA (nOVAmax) were performed before mice were immunized with or without gastric acid‐suppression medication. Antibody levels, regulatory T‐cell (Treg) numbers, and cytokine levels were evaluated. Human moDCs or PBMCs were incubated with proteins and evaluated for expression of surface markers, cytokine production, and proliferation of Th2 as well as Tregs. Results: In contrast to OVA and nOVA, the conformation of nOVAmax was substantially changed. nOVAmax pretreated mice had decreased IgE as well as IgG1 and IgG2a levels and Treg numbers were significantly elevated, while cytokine levels remained at baseline level. nOVAmax induced a regulatory DC phenotype evidenced by a decrease of the activation marker CD86 and an increase in IL‐10 production and was associated with a higher proliferation of memory Tregs. Conclusion: Oral pretreatment with highly nitrated proteins induces a tolerogenic immune response in the food allergy model and in human immune cells. Abstract : Oral pre‐exposure to highly nitrated food proteins is associated with prevention of food allergy development and immune tolerance as evidenced by suppressed allergen‐specific IgE levels and enhanced Tregs. A regulatory moDC phenotype indicated by low expression of costimulatory molecules and higher secretion of IL‐10 was observed after pre‐incubation with highly nitrated proteins. Secondary protein structure of highly nitrated allergens is substantially altered potentially being associated with the capacity to induce a tolerogenic immune response. OVA: ovalbumin; PBMCs, peripheral blood mononuclear cells; TNM, tetranitromethane