Dendritic cells--at the front-line of pathogen attack.

Efficient immune defence function is dependent on the role played by dendritic cells (DCs), particularly the interaction between conventional DC (cDC) and plasmacytoid DC (pDC), together with other monocytic cells. This functionality of immune defences is open to manipulation by viral pathogens infecting DC, a situation further complicated by the diversity of mechanisms employed by different viruses and the subset of DC involved. The present review uses two virus examples--classical swine fever virus (CSFV) and porcine circovirus type 2 (PCV2)--to demonstrate the complexity of this host-pathogen scenario. CSFV is a monocytotropic RNA virus infecting and replicating in both cDC and pDC. This virus employs its non-structural Npro protein for antagonizing the Type I interferon (IFN) induction pathway. The Npro protein promotes proteasomal degradation of interferon regulatory factor (IRF)3, particularly notable in cDC. In contrast, CSFV infection induces IFNalpha production by pDC, probably due to a lack of interference by the Npro protein with the IRF7 more prominent in pDC. Such ability of the virus to inhibit cDC while augmenting IFNalpha production by pDC might lead to an exaggerated pDC response, relating to the immunopathological characteristics of the disease. PCV2 is an ssDNA containing virus, which in contrast to CSFV is inefficient in its capacity to replicate in DC. Recent evidence suggests that virus replication occurs in endothelial cells, with the DC being more involved through their particularly elevated endocytosis of the virus. PCV2 can accumulate to high levels both in vitro and in vivo, a phenomenon dependent on the virus capsid protein, inferring that the viral capsid or genome impedes DC endocytic degradation of the virus. Nevertheless, the presence of PCV2 in cDC does not interfere with processing of other antigens. The immunoregulatory characteristics of PCV2 are manifest as impairment of "danger" recognition by cells of the innate defences. This varies dependent on the "danger" signal and the cells responding, especially when one compares cDC and pDC. Overall, the PCV2-induced immunomodulation contrasts with that of CSFV in being a property dependent on the viral genome, particularly the dsDNA replicative form, and with immunoregulatory capacity for both cDC and pDC. Moreover, PCV2 compromises immune defence development against other pathogens rather than itself. In conclusion, the DC family represents a critical immune defence element open to modulation by virus infection, with serious consequences for host resistance to disease. The characteristics of the immune modulation depend on the virus and the DC subsets involved. Overall, the roles played by the pDC can be decisive in shaping the outcome of the infection and the characteristics of the virus-induced immunocompromisation.