Cellular and Molecular Immunology, GIGA-Research, University of Liège, Liège, Belgium.
Eur J Immunol. 2014 Dec;44(12):3585-95. doi: 10.1002/eji.201444594. Epub 2014 Nov 7.
Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since NK cells collaborate with dendritic cells (DCs) to induce an immune response against viral infections and tumors, we studied the impact of this crosstalk in the context of HPV vaccination. NK cells in the presence of HPV-VLPs enhanced DC-maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10. This activation was bidirectional. Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLA-DR). The function of NK cells was also improved as shown by an increase in IFN-γ secretion and cytotoxic activity against an HPV(+) cell line. This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated. Our results provide insight into how VLPs interact with innate immune cells and how NK cells and DCs play a role in the immune response induced by this vaccine agent.
病毒样颗粒（VLPs）的人乳头瘤病毒（HPV）被用作疫苗，以预防 HPV 引起的癌症，最近我们已经表明，这些 VLPs 能够激活自然杀伤（NK）细胞。由于 NK 细胞与树突状细胞（DCs）合作，引发针对病毒感染和肿瘤的免疫反应，我们研究了这种串扰在 HPV 疫苗接种背景下的影响。如 CD86 和 HLA-DR 的上调以及 IL-12p70 的增加，但不是免疫抑制细胞因子 IL-10 的增加所表明的那样，存在 HPV-VLPs 时，NK 细胞增强了 DC 的成熟。这种激活是双向的。实际上，在存在 HPV-VLPs 的情况下，DC 进一步通过诱导细胞表面激活标志物（CD69 和 HLA-DR）的上调来激活 NK 细胞。NK 细胞的功能也得到了改善，表现为 IFN-γ 分泌的增加和对 HPV(+)细胞系的细胞毒性活性。NK 细胞和 DC 之间的这种串扰需要 CD40 相互作用和 IL-12p70 的分泌，而 NKG2D 则没有参与。我们的研究结果深入了解了 VLPs 如何与先天免疫细胞相互作用，以及 NK 细胞和 DCs如何在这种疫苗诱导的免疫反应中发挥作用。
