College of Animal Science and Technology, Beijing University of Agriculture, No. 7 Beinong Road, Changping District, Beijing, 102206, China.
Beijing Key Laboratory of TCVM, Beijing University of Agriculture, No. 7 Beinong Road, Changping District, Beijing, 102206, China.
Virol J. 2019 Dec 12;16(1):154. doi: 10.1186/s12985-019-1256-z.
Porcine circovirus (PCV) disease caused by PCV type 2 (PCV2) is mainly attributed to immunosuppression and immune damage. PCV2 can infect vascular endothelial cells and induce high expression of endothelial IL-8. Dendritic cells (DCs), as professional antigen-presenting cells, can not only present antigens but also activate naïve T-cells, causing an immune response.
To demonstrate whether endothelial IL-8 is the main factor inhibiting the maturation and related functions of dendritic cells during PCV2 infection, monocyte-derived DCs (MoDCs) and porcine iliac artery endothelial cells (PIECs) processed by different methods were co-cultured in two ways. Flow cytometry, molecular probe labeling, fluorescence quantitative PCR, and the MTS assay were used to detect the changes in related functions and molecules of MoDCs.
Compared to those in the PIEC-DC group, the endothelial IL-8 upregulation co-culture group showed significantly lower double-positive rates for CD80/86 and MHC-II of MoDCs and significantly increased endocytosis of MoDCs. Meanwhile, the adhesion rate and average fluorescence intensity of MoDCs were significantly downregulated in migration and adhesion experiments. Furthermore, the MHC-I and LAMP7 mRNA levels in MoDCs and the proliferation of MoDC-stimulated T-cells were markedly reduced. However, the changes in MoDCs of the endothelial IL-8 downregulation co-culture group were the opposite.
PCV2-induced endothelial IL-8 reduces the adhesion and migration ability of MoDCs, resulting in a decreased maturation rate of MoDCs, and further inhibits antigen presentation by DCs. These results may explain the immunosuppressive mechanism of PCV2 from the perspective of the interaction between endothelial cells and DCs in vitro.
由猪圆环病毒 2 型（PCV2）引起的猪圆环病毒病主要归因于免疫抑制和免疫损伤。PCV2 可以感染血管内皮细胞，并诱导内皮白细胞介素-8（IL-8）的高表达。树突状细胞（DCs）作为专业的抗原提呈细胞，不仅可以提呈抗原，还可以激活初始 T 细胞，引发免疫反应。
为了证明内皮细胞 IL-8 是否是 PCV2 感染期间抑制树突状细胞成熟和相关功能的主要因素，采用不同方法处理单核细胞来源的树突状细胞（MoDCs）和猪髂动脉内皮细胞（PIECs），以两种方式进行共培养。采用流式细胞术、分子探针标记、荧光定量 PCR 和 MTS 测定法检测 MoDCs 相关功能和分子的变化。
与 PIEC-DC 组相比，内皮细胞 IL-8 上调共培养组 MoDCs 的 CD80/86 和 MHC-II 双阳性率显著降低，内吞作用显著增强。同时，迁移和黏附实验中 MoDCs 的黏附率和平均荧光强度显著下调。此外，MoDCs 中 MHC-I 和 LAMP7mRNA 水平以及 MoDC 刺激的 T 细胞增殖明显降低。然而，内皮细胞 IL-8 下调共培养组 MoDCs 的变化则相反。
PCV2 诱导的内皮细胞 IL-8 降低了 MoDCs 的黏附和迁移能力，导致 MoDCs 的成熟率降低，并进一步抑制 DCs 的抗原呈递。这些结果可能从体外内皮细胞和 DCs 相互作用的角度解释了 PCV2 的免疫抑制机制。
