A crucial function of IFN-I is their ability to inhibit viral replication and dissemination [16] . Indeed, pDC depletion leads to enhanced local HSV-2 replication in mice infected intra-vaginally [46] and in the spleen or liver in animals infected intravenously [3] , correlating with the major role of pDCs for local versus systemic IFN-I production in these experimental settings. Thus, pDC-derived IFN-I directly contributes to the control of HSV-2 replication in vivo in mice upon systemic or local infections. However, the picture appears much more complex for MCMV infection. In 129Sv mice, pDC-derived IFN-I likely contribute to MCMV control as anti-GR1 [12] or anti-BST2 (data not shown) antibody-mediated pDC depletion leads to a higher splenic viral load. In C57BL/6 mice, different approaches used to selectively affect pDC functions have led to different results. In vivo anti-GR1 [12] or anti-BST2 [39] antibody-mediated pDC depletion has no significant impact on viral replication in the spleen. Because this treatment is less efficient than in 129 mice (data not shown), it is not possible to rule out that residual pDCs still contribute sufficient IFN-I production to allow maximal antiviral effects. This interpretation could be consistent with the observation that complete abrogation of pDC IFN-I production in C57BL/6 mice leads to a significant increase in MCMV replication or in viral-induced mortality, as reported in the Ik L/L mice which lack mature pDCs [45] or in interferonregulatory factor 7 (IRF7) -/mice which have lost pDC ability to produce IFN-I [52]. However, because pDCs are not the only cell type affected in these two mutant mouse models, the interpretation of their phenotype is difficult. An alternative explanation for the differential impact of pDC depletion on MCMV replication in 129Sv versus C57BL/6 mice could be the specific capacity of the latter to mount other innate immune responses redundant for this function. Indeed, contrary to 129Sv mice, C57BL/6 mice have efficient anti-MCMV natural killer (NK) cell responses which are able to recognize and kill infected cells in vivo very rapidly after infection at the same time as pDCs are activated for IFN-I production [53] . This antiviral function of NK cells depends on their activation by IFN-I [22] . Thus, in C57BL/6 mice but not in 129Sv animals, low levels of residual IFN-I may be sufficient to promote efficient viral control by NK cells, even in the absence of strong direct antiviral effects of IFN-I, and irrespective of the cellular source of these cytokines.