The selection during evolution of a cell type specialized for IFN-I production in response to viral infection may seem paradoxical with the fact that, when productively infected, any cell type is theoretically capable of producing high levels of these cytokines, including cDCs [98] . However, the major differences between pDCs and other cell types in the molecular mechanisms in place for the sensing of the viral infections and for the downstream induction of IFN-I production are revealing. Indeed, in most instances, pDC IFN-I production does not require endogenous viral replication in the cytoplasm but only detection in endosomes of engulfed oligonucleotides derived from other infected cells or viral particles. In fact, pDCs appear resistant to productive viral infection by several herpesviruses. In addition, IFN-I production by pDCs is not strongly dependent on a positive feedback loop, because pDCs constitutively express IRF7 at very high levels. In contrast, IFN-I production by most other cell types requires detection of viral RNA or DNA in the cytoplasm, and hence endogenous productive viral replication. Under these conditions, viruses have evolved a variety of strategies to inhibit both IFN-I production and IFN-I responses in infected cells very early on after initiation of their replication [87, [99] [100] [101] . Therefore, in infected cells, viruses do not only interfere with the intensity of the first wave of IFN-β/α4 but also greatly compromise the amplification loop for secondary induction of the other subtypes of IFN-α. It should be noted that HCMV has recently been reported to suppress IFN-I secretion by pDCs through its interleukin 10 homolog [102] . Nevertheless, pDCs may have a non redundant role in the rapid systemic production of IFN-I and the consecutive induction of a global innate antiviral state in the host under defined conditions of infection with herpesviruses, due to their general ability to escape viral interference with these functions.