Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Department of Biosciences, University of Salzburg, Salzburg, Austria.
Allergy. 2020 Feb;75(2):412-422. doi: 10.1111/all.14030. Epub 2019 Oct 1.
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.
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.
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.
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.
Oral pretreatment with highly nitrated proteins induces a tolerogenic immune response in the food allergy model and in human immune cells.
食物过敏与较高的个人健康和经济负担相关。为了实现免疫耐受的调节，食物化合物可以通过化学修饰，例如通过翻译后蛋白质硝化，这也可以通过胃肠道中的饮食衍生硝化剂发生。
我们旨在分析预处理硝化食物蛋白对小鼠食物过敏模型中的免疫反应以及对人单核细胞来源的树突状细胞（moDC）和 PBMC 的影响。
模型过敏原卵清蛋白（OVA）以不同的硝化程度硝化，通过圆二色性（CD）测定蛋白质的二级结构。在未用或用胃酸抑制药物免疫之前，用 OVA、硝化 OVA（nOVA）和最大硝化 OVA（nOVAmax）进行过敏预防治疗。评估抗体水平、调节性 T 细胞（Treg）数量和细胞因子水平。用蛋白质孵育人 moDC 或 PBMC，并评估表面标志物的表达、细胞因子产生以及 Th2 和 Treg 的增殖。
与 OVA 和 nOVA 相比，nOVAmax 的构象发生了实质性变化。nOVAmax 预处理的小鼠 IgE 以及 IgG1 和 IgG2a 水平降低，Treg 数量显著升高，而细胞因子水平保持在基线水平。nOVAmax 诱导了调节性 DC 表型，表现为激活标志物 CD86 减少和 IL-10 产生增加，并与记忆性 Treg 的增殖增加相关。
口服预处理高度硝化的蛋白质可在食物过敏模型和人类免疫细胞中诱导耐受免疫反应。
