Endothelial IL-8 induced by porcine circovirus type 2 affects dendritic cell maturation and antigen-presenting function

Abstract

BackgroundPorcine 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.MethodsTo 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.ResultsCompared 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.ConclusionsPCV2-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.

Porcine circovirus type 2 upregulates endothelial-derived IL-8 production in porcine iliac artery endothelial cells via the RIG-I/MDA-5/MAVS/JNK signaling pathway

“…It is reported that endothelial-derived IL-8, with a pentapeptide AVLPR extension at the NH2-terminus [5], has different biological function compared with monocyte-derived IL-8 [6]. Our previous reports also showed that the endothelial IL-8 upregulated by PCV2 infection could inhibit the maturation and antigen presentation of dendritic cells [4,7].…”

Annexin‐1 is an oncogene in glioblastoma and causes tumour immune escape through the indirect upregulation of interleukin‐8

“…Previous studies have shown that ANXA1 is either upregulated in tumours such as gastric cancer, 17 , 18 , 19 , 20 pancreatic carcinoma 21 and lung cancer 22 and correlated with poor prognosis or downregulated in tumours such as head and neck squamous cell carcinoma 23 and nasopharyngeal carcinoma. 24 Typically, studies have focused on the effects of ANXA1 binding to the FPR receptor.…”

“…Generally, IL‐8 gene expression is regulated by the transcriptional activation of nuclear factor‐kB (NF‐κB), which is suggested to be mainly associated with the binding between the minimal promoter region of IL‐8 and the p65 or cRel homodimers of NF‐κB 15,16 . Recently, it was found that IL‐8 could affect dendritic cell (DC) maturation by retaining DCs in tumours and blocking the migration capacity of DCs from initial inflammation sites to draining lymph nodes, affecting its antigen‐presenting function in tumours 17–19 . Based on the literature and previous reports, we hypothesized that NF‐κB (p65) hyperactivation mediated by ANXA1 is partly responsible for IL‐8 overexpression, which inhibits DC maturation in GBM.…”

“…15 , 16 Recently, it was found that IL‐8 could affect dendritic cell (DC) maturation by retaining DCs in tumours and blocking the migration capacity of DCs from initial inflammation sites to draining lymph nodes, affecting its antigen‐presenting function in tumours. 17 , 18 , 19 Based on the literature and previous reports, we hypothesized that NF‐κB (p65) hyperactivation mediated by ANXA1 is partly responsible for IL‐8 overexpression, which inhibits DC maturation in GBM.…”

Advances in Crosstalk between Porcine Circoviruses and Host

“…On the contrary, PCV2 enhances the expression of the suppressor of cytokine signaling 3 (SOCS3), which further interacts with STAT3 and TNF-associated receptor-associated factor 2 (TRAF2), resulting in subclinical infection characterized by downregulation of IL-6 and TNF-α signaling [ 142 ]. Furthermore, PCV2-induced endothelial IL-8 decreases the adhesion and migration of monocyte-derived DCs (MoDCs), resulting in a decrease in the maturation rate of MoDCs and further inhibition of antigen presentation by dendritic cells (DCs) [ 143 ]. Moreover, the PKR signaling pathway was activated by dsRNA generated during PCV transcription, which activates eIF2α to inhibit virus protein [ 70 , 144 ].…”