Vincent Isabelle E, Carrasco Carlos P, Guzylack-Piriou Laurence, Herrmann Brigitte, McNeilly Francis, Allan Gordon M, Summerfield Artur, McCullough Kenneth C
Institute of Virology and Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland.
Immunology. 2005 Jul;115(3):388-98. doi: 10.1111/j.1365-2567.2005.02165.x.
Viral interactions with dendritic cells (DCs) have important consequences for immune defence function. Certain single-stranded DNA viruses that associate with a number of species, including humans and pigs, exhibit interesting characteristics in this context. Porcine circovirus type 2 (PCV2) can persist within myeloid DCs in the absence of virus replication. Internalization was observed with both conventional blood DCs and plasmacytoid DCs [natural interferon-producing cells (NIPCs)], as well as DC precursors. This PCV2-DC interaction neither induced nor inhibited DC differentiation. The maturation of myeloid DCs induced by a cocktail of interferon-alpha/tumour necrosis factor-alpha (IFN-alpha/TNF-alpha), and the ability to process and present antigen to T lymphocytes, remained intact in the presence of PCV2. The virus was clearly internalized by the DCs, a process noted with both mature and immature cells. This suggested a non-macropinocytic uptake, confirmed by an insensitivity to wortmannin but sensitivity to cytochalasin D, chlorpromazine and bafilomycin. Nevertheless, PCV2 was immunomodulatory, being effected through the reaction of NIPC to danger signals. When NIPCs responded to the CpG-oligonucleotide (CpG-ODN), their costimulatory function which induces myeloid DC maturation was clearly impaired by the presence of PCV2. This was caused by a PCV2-induced inhibition of the IFN-alpha and TNF-alpha normally produced following interaction with CpG-ODN. Thus, the immunomodulatory activity of PCV2 is mediated through the disruption of NIPC function. This would impair the maturation of associated myeloid DC and have major implications for the efficient recognition of viral and bacterial danger signals, favouring the establishment of infections additional to that of PCV2.
病毒与树突状细胞（DCs）的相互作用对免疫防御功能具有重要影响。某些与包括人类和猪在内的多种物种相关的单链DNA病毒，在这种情况下表现出有趣的特征。猪圆环病毒2型（PCV2）在无病毒复制的情况下可在髓样DCs内持续存在。在传统血液DCs、浆细胞样DCs[天然干扰素产生细胞（NIPCs）]以及DC前体细胞中均观察到内化现象。这种PCV2-DC相互作用既不诱导也不抑制DC分化。在存在PCV2的情况下，由干扰素-α/肿瘤坏死因子-α（IFN-α/TNF-α）混合物诱导的髓样DCs成熟以及处理和呈递抗原给T淋巴细胞的能力保持完整。DCs能够明显内化该病毒，成熟和未成熟细胞均可观察到这一过程。这表明其摄取方式不是巨吞饮作用，对渥曼青霉素不敏感但对细胞松弛素D、氯丙嗪和巴弗洛霉素敏感可证实这一点。然而，PCV2具有免疫调节作用，是通过NIPCs对危险信号的反应来实现的。当NIPCs对CpG寡核苷酸（CpG-ODN）作出反应时，PCV2的存在会明显损害其诱导髓样DC成熟的共刺激功能。这是由PCV2诱导抑制通常在与CpG-ODN相互作用后产生的IFN-α和TNF-α所致。因此，PCV2的免疫调节活性是通过破坏NIPC功能介导的。这将损害相关髓样DC的成熟，并对有效识别病毒和细菌危险信号产生重大影响，有利于除PCV2感染之外其他感染的建立。
