在过敏反应的背景下,关于硅纳米颗粒-过敏原相互作用对抗原呈递细胞功能的机制见解。
Mechanistic insights into silica nanoparticle-allergen interactions on antigen presenting cell function in the context of allergic reactions.
机构信息
Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria.
出版信息
Nanoscale. 2023 Feb 2;15(5):2262-2275. doi: 10.1039/d2nr05181h.
The incorporation of nanomaterials into consumer products has substantially increased in recent years, raising concerns about their safety. The inherent physicochemical properties of nanoparticles allow them to cross epithelial barriers and gain access to immunocompetent cells. Nanoparticles in cosmetic products can potentially interact with environmental allergens, forming a protein corona, and together penetrate through damaged skin. Allergen-nanoparticle interactions may influence the immune response, eventually resulting in an adverse or beneficial outcome in terms of allergic reactivity. This study determines the impact of silica nanoparticle-allergen interactions on allergic sensitization by studying the major molecular mechanisms affecting allergic responses. The major birch pollen allergen Bet v 1 was chosen as a model allergen and the birch pollen extract as a comparator. Key events in immunotoxicity including allergen uptake, processing, presentation, expression of costimulatory molecules and cytokine release were studied in human monocyte-derived dendritic cells. Using an sensitization model, murine Bet v 1-specific IgG and IgE levels were monitored. Upon the interaction of allergens with silica nanoparticles, we observed an enhanced uptake of the allergen by macropinocytosis, improved proteolytic processing, and presentation concomitant with a propensity to increase allergen-specific IgG2a and decrease IgE antibody levels. Together, these events suggest that upon nanoparticle interactions the immune response is biased towards a type 1 inflammatory profile, characterized by the upregulation of T helper 1 (Th1) cells. In conclusion, the interaction of the birch pollen allergen with silica nanoparticles will not worsen allergic sensitization, a state of type 2-inflammation, but rather seems to decrease it by skewing towards a Th1-dominated immune response.
近年来,纳米材料在消费产品中的应用大量增加,引发了人们对其安全性的担忧。纳米颗粒的固有物理化学性质使其能够穿透上皮屏障并进入免疫活性细胞。化妆品中的纳米颗粒可能与环境过敏原相互作用,形成蛋白质冠,并一起穿透受损的皮肤。过敏原-纳米颗粒的相互作用可能会影响免疫反应,最终导致过敏反应的不利或有利结果。本研究通过研究影响过敏反应的主要分子机制,确定了纳米颗粒-过敏原相互作用对过敏致敏的影响。选择主要的桦树花粉过敏原 Bet v 1 作为模型过敏原,桦树花粉提取物作为对照。研究了影响免疫毒性的主要事件,包括过敏原摄取、加工、呈递、共刺激分子表达和细胞因子释放,在人单核细胞衍生的树突状细胞中进行。使用 致敏模型,监测了小鼠 Bet v 1 特异性 IgG 和 IgE 水平。当过敏原与二氧化硅纳米颗粒相互作用时,我们观察到过敏原通过巨胞饮作用被增强摄取,蛋白水解加工得到改善,并与增加过敏原特异性 IgG2a 和减少 IgE 抗体水平的趋势相一致。总之,这些事件表明,在纳米颗粒相互作用下,免疫反应偏向于 1 型炎症表型,其特征是 T 辅助 1(Th1)细胞的上调。总之,桦树花粉过敏原与二氧化硅纳米颗粒的相互作用不会加重过敏致敏,即 2 型炎症状态,而是通过偏向 Th1 主导的免疫反应似乎会减轻过敏致敏。
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