Type-A CpG oligonucleotides activate exclusively porcine natural interferon-producing cells to secrete interferon-α, tumour necrosis factor-α and interleukin-12
Type-A CpG oligonucleotides activate exclusively porcine natural interferon-producing cells to secrete interferon-α, tumour necrosis factor-α and interleukin-12
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DOI：
10.1111/j.1365-2567.2004.01856.x
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发表时间：
2004-05-01
期刊：
影响因子：
6.4
通讯作者：
Summerfield, A
中科院分区：
文献类型：
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作者：
Guzylack-Piriou, L;Balmelli, C;Summerfield, A
天然干扰素产生细胞（NIPC），也被称为未成熟浆细胞样树突状细胞（PDC），构成一小群白细胞，分泌高水平的I型干扰素，以响应某些危险信号。这些信号中包括那些来自含有未甲基化CpG基序的DNA的信号。本研究表明，CpG寡核苷酸（CpG- odn） 2216、D32和D19可诱导猪外周血单个核细胞（PBMCs）产生大量的干扰素- α (ifn - α)、肿瘤坏死因子- α (tnf - α)和白细胞介素-12。猪车间集群3 (SWC3)（低）CD4（高）细胞，具有高il -3结合活性，代表NIPC，是唯一响应CpG-ODN的细胞因子产生细胞。这些细胞不表达CD6、CD8或CD45RA。重要的是，单核细胞来源的DC不通过分泌ifn - α或tnf - α或上调共刺激分子表达来响应CpG-ODN。CpG-ODN上调MHCⅱ类和CD80/86在NIPC上的表达，但不能促进NIPC存活。有趣的是，某些不能诱导NIPC分泌ifn - α或上调MHC II类和CD80/86的CpC-ODN确实促进了NIPC的活力。综上所述，CpG-ODN对猪NIPC、单核细胞和髓系dc的影响与其对人类同类细胞的影响相关。这些结果为CpG-ODN作为佐剂用于新型疫苗的研制提供了重要的基础，并证明了猪作为这种方法的替代动物模型的重要性。
Natural interferon-producing cells (NIPC), also referred to as immature plasmacytoid dendritic cells (PDC), constitute a small population of leucocytes secreting high levels of type I interferons in response to certain danger signals. Amongst these signals are those from DNA containing unmethylated CpG motifs. The present work demonstrated that the CpG oligonucleotides (CpG-ODN) 2216, D32 and D19 induce high amounts of interferon-alpha (IFN-alpha), tumour-necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12 in porcine peripheral blood mononuclear cells (PBMCs). Swine workshop cluster 3 (SWC3)(low) CD4(high) cells, with high IL-3-binding activity, representing NIPC, were the exclusive cytokine-producing cells responding to the CpG-ODN. These cells did not express CD6, CD8 or CD45RA. Importantly, monocyte-derived DC did not respond to CpG-ODN by secretion of IFN-alpha or TNF-alpha or by the up-regulation of costimulatory molecule expression. CpG-ODN up-regulated MHC class II and CD80/86 expression on the NIPC, but were unable to promote NIPC survival. Interestingly, certain CpC-ODN, incapable of inducing NIPC to secrete IFN-alpha or up-regulate MHC class II and CD80/86, did promote NIPC viability. Taken together, the influence of CpG-ODN on porcine NIPC, monocytes and myeloid DCs relates to that observed with their human equivalents. These results represent an important basis for the application of CpG-ODN as adjuvants for the formulation of novel vaccines and demonstrate the importance of the pig as an alternative animal model for this approach.