The large-scale utilization of nanotechnology depends on public and consumer confidence in the safety of this new technology. Studying the interaction of nanoparticles with immune cells plays a vital role in the safety assessment of nanomedicine. Although some researches have indicated that the immune cells undergo severe interfere after phagocytosis of nanoparticles, the impact on immune system of the whole body are still unclear. Here, we use immune cells labeled transgenic zebrafish to study the mechanisms of nanoparticles on zebrafish immune cells. We demonstrate that gold nanoparticles (Au NPs) phagocytized by immune cells can reduce and retard the sensitivity of immune response, resulting nanoparticle-induced bluntness in immune cell (NIBIC). RNA-seq and functional analysis reveal that NIBIC is mainly induced by the inhibiting expression of chemokine receptor 5 (CCR5). Furthermore, PVP-modified Au NPs can eliminate NIBIC by inhibiting the cell phagocytosis. Our results highlight the potential risk for Au NPs in vivo and further the understanding of the mechanism of the interaction between Au NPs and the immune response. We should consider this factor in future material design and pay more attention to the process of using nanomedicines on immune diseases.

纳米技术的大规模利用取决于公众和消费者对这项新技术安全性的信心。研究纳米粒子与免疫细胞的相互作用在纳米药物安全性评估中起着至关重要的作用。尽管一些研究表明，纳米颗粒被吞噬后免疫细胞会受到严重干扰，但对全身免疫系统的影响仍不清楚。在这里，我们使用标记为转基因斑马鱼的免疫细胞来研究纳米颗粒对斑马鱼免疫细胞的作用机制。我们证明了被免疫细胞吞噬的金纳米颗粒（Au NPs）可以减少和延迟免疫反应的敏感性，从而导致纳米颗粒在免疫细胞（NIBIC）中引起钝性。RNA-seq和功能分析表明，NIBIC主要是由趋化因子受体5（CCR5）的表达抑制引起的。此外，PVP修饰的金纳米粒子可以通过抑制细胞吞噬作用消除NIBIC。我们的结果强调了金纳米颗粒的潜在风险体内和进一步了解金纳米颗粒之间的相互作用和免疫反应的机制。我们应该在将来的材料设计中考虑这个因素，并更多地关注使用纳米药物治疗免疫疾病的过程。