Malachin Giulia, Lubian Elisa, Mancin Fabrizio, Papini Emanuele, Tavano Regina
Department of Biomedical Sciences, University of Padua, Padua, Italy.
Department of Chemical Sciences, University of Padua, Padua, Italy.
Clin Vaccine Immunol. 2017 Oct 5;24(10). doi: 10.1128/CVI.00178-17. Print 2017 Oct.
Dendritic cells (DCs) regulate the host-microbe balance in the gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food, and cosmetics. We analyzed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal bacteria (, ) or pathogenic bacteria (, ) in the presence of amorphous silica nanoparticles (SiO NPs). EMs and NPs synergistically increased the levels of cytotoxicity and cytokine production, with different nanoparticle dose-response characteristics being found, depending on the bacterial species. and EMs plus NPs at nontoxic doses stimulated the secretion of interleukin-1β (IL-1β), IL-12, IL-10, and IL-6, while and EMs plus NPs at toxic doses stimulated the secretion of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, and IL-5. On the contrary, and EMs induced cytokines only when they were combined with NPs at toxic concentrations. The induction of maturation markers (CD86, CD80, CD83, intercellular adhesion molecule 1, and major histocompatibility complex class II) by commensal bacteria but not by pathogenic ones was improved in the presence of noncytotoxic SiO NP doses. DCs consistently supported the proliferation and differentiation of CD4 and CD8 T cells secreting IFN-γ and IL-17A. The synergistic induction of CD86 was due to nonprotein molecules present in the EMs from all bacteria tested. At variance with this finding, the synergistic induction of IL-1β was prevalently mediated by proteins in the case of EMs and by nonproteins in the case of EMs. A bacterial costimulus did not act on DCs after adsorption on SiO NPs but rather acted as an independent agonist. The inflammatory and immune actions of DCs stimulated by commensal bacterial agonists might be altered by the simultaneous exposure to engineered or environmental NPs.
树突状细胞（DCs）调节肠道和皮肤中的宿主 - 微生物平衡，这些组织可能会接触到药物、食品和化妆品中存在的纳米颗粒（NPs）。我们分析了在无定形二氧化硅纳米颗粒（SiO NPs）存在的情况下，与从共生细菌（ ， ）或致病细菌（ ， ）培养物中获得的细胞外培养基（EMs）一起孵育的DCs的活力和活化情况。EMs和NPs协同增加细胞毒性和细胞因子产生水平，根据细菌种类发现了不同的纳米颗粒剂量 - 反应特征。无毒剂量的 和 EMs加NPs刺激白细胞介素 - 1β（IL - 1β）、IL - 12、IL - 10和IL - 6的分泌，而有毒剂量的 和 EMs加NPs刺激γ干扰素（IFN - γ）、肿瘤坏死因子α（TNF - α）、IL - 4和IL - 5的分泌。相反， 和 EMs仅在与有毒浓度的NPs结合时才诱导细胞因子。在无细胞毒性的SiO NP剂量存在下，共生细菌而非致病细菌对成熟标志物（CD86、CD80、CD83、细胞间粘附分子1和主要组织相容性复合体II类）的诱导作用得到改善。DCs持续支持分泌IFN - γ和IL - 17A的CD4和CD8 T细胞的增殖和分化。CD86的协同诱导是由于所有测试细菌的EMs中存在的非蛋白质分子。与这一发现不同的是，IL - 1β的协同诱导在 EMs的情况下主要由蛋白质介导，而在 EMs的情况下由非蛋白质介导。细菌共刺激剂在吸附到SiO NPs上后不对DCs起作用，而是作为独立的激动剂起作用。共生细菌激动剂刺激的DCs的炎症和免疫作用可能会因同时接触工程纳米颗粒或环境纳米颗粒而改变。
