Université Paris-Saclay, Inserm, Inflammation, Microbiome and Immunosurveillance, 92290 Châtenay-Malabry, France.
Université Paris-Saclay, CNRS, Institut Galien Paris Saclay, 92296 Châtenay-Malabry, France.
Toxicol Sci. 2021 Dec 28;185(1):105-116. doi: 10.1093/toxsci/kfab120.
Innate immune cells such as dendritic cells (DCs) sense and engulf nanomaterials potentially leading to an adverse immune response. Indeed, as described for combustion-derived particles, nanomaterials could be sensed as danger signals, enabling DCs to undergo a maturation process, migrate to regional lymph nodes and activate naive T lymphocytes. Synthetic amorphous silica nanoparticles (SAS-NPs) are widely used as food additives, cosmetics, and construction materials. This work aimed to evaluate in vitro the effects of manufactured SAS-NPs, produced by thermal or wet routes, on human DCs functions and T-cell activation. Human monocyte-derived DCs (moDCs) were exposed for 16 h to 3 endotoxin-free test materials: fumed silica NPs from Sigma-Aldrich (no. S5505) or the JRC Nanomaterial Repository (NM-202) and colloidal LudoxTMA NPs. Cell viability, phenotypical changes, cytokines production, internalization, and allogeneic CD4+ T-cells proliferation were evaluated. Our results showed that all SAS-NPs significantly upregulated the surface expression of CD86 and CD83 activation markers. Secretions of pro-inflammatory cytokines (CXCL-8 and CXCL-12) were significantly enhanced in a dose-dependent manner in the moDCs culture supernatants by all SAS-NPs tested. In an allogeneic coculture, fumed silica-activated moDCs significantly increased T-lymphocyte proliferation at all T-cell: DC ratios compared with unloaded moDCs. Moreover, analysis of coculture supernatants regarding the production of T-cell-derived cytokines showed a significant increase of IL-9 and IL-17A and F, as well as an upregulation of IL-5, consistent with the pro-inflammatory phenotype of treated moDCs. Taken together, these results suggest that SAS-NPs could induce functional moDCs maturation and play a role in the immunization process against environmental antigens.
先天免疫细胞，如树突状细胞 (DCs)，能够感知和吞噬纳米材料，从而可能引发不良反应。事实上，正如描述的那样，燃烧衍生颗粒的纳米材料可以被视为危险信号，使 DC 经历成熟过程，迁移到区域淋巴结并激活幼稚 T 淋巴细胞。合成无定形二氧化硅纳米颗粒 (SAS-NPs) 被广泛用作食品添加剂、化妆品和建筑材料。本工作旨在评估通过热或湿途径制造的 SAS-NPs 对人 DC 功能和 T 细胞激活的体外影响。用 3 种无内毒素测试材料暴露人单核细胞衍生的 DC（moDCs）16 小时：来自西格玛-奥德里奇的气相法二氧化硅 NPs（no. S5505）或 JRC 纳米材料库（NM-202）和胶体 LudoxTMA NPs。评估细胞活力、表型变化、细胞因子产生、内化和同种异体 CD4+T 细胞增殖。结果表明，所有 SAS-NPs 均显著上调了 CD86 和 CD83 激活标志物的表面表达。所有测试的 SAS-NPs 均以剂量依赖的方式显著增强了 moDCs 培养上清液中促炎细胞因子 (CXCL-8 和 CXCL-12) 的分泌。在同种异体共培养中，与未加载的 moDCs 相比，气相聚硅氮烷激活的 moDCs 显著增加了所有 T 细胞：DC 比例下的 T 淋巴细胞增殖。此外，关于共培养上清液中 T 细胞衍生细胞因子产生的分析表明，IL-9 和 IL-17A 和 F 的产生显著增加，以及 IL-5 的上调，与处理后的 moDCs 的促炎表型一致。总之，这些结果表明 SAS-NPs 可诱导功能性 moDCs 成熟，并在针对环境抗原的免疫过程中发挥作用。
