Fig. 1

Speculated involvement of natural interferon producing cells (NIPCs) and monocytes/macrophages in the pathogenesis of PCVAD induced by co-infection with PCV2 and other pathogens. PCV2 DNA has been reported to interfere with the response of NIPCs to pathogenic cytosine-phosphorothioate-guanine-oligodeoxynucleotides (CpG-ODNs) and hence suppress the production of IFN-α and TNF-α. On the other hand, PCV2 infection impairs the phagocytic and microbicidal ability of macrophages. These findings indicate that interactions of PCV2 with NIPCs and macrophages render host more susceptible to concurrent or secondary infection. Considering that the replication of PCV2 in macrophages is proposed to be achievable in vitro using appropriate stimulatory signals (such as the liposaccharide signal) and that it leads to the accumulation of the viral antigen, it can be speculated that immune stimulation by infection or vaccination promotes PCV2 replication in lymphoid tissues, which may provide a good explanation of PCVAD development following co-infection of PCV2 with other viral or bacterial pathogens rather than by PCV2 infection alone. In addition, interaction of monocyte/macrophage cell lineages with PCV2 plays an important role in mediating granulomatous lesions in lymph nodes and inducing PCVAD. Macrophages are recognized to be the primary cell source of MCP-1 and MIP-1, and it is suggested that MCP-1 and MIP-1 expression could be directly induced by PCV2 infection. Given that MCP-1 and MIP-1 have effective chemoattractant and activating effects on monocytes, high levels of both were speculated to largely facilitate the recruitment of monocytes from blood. The greater number of monocytes recruited to lymphoid tissues can in turn further augment and amplify cytokine secretion and cell recruitment, subsequently inducing granulomatous inflammation and leading to PCVAD