Our results demonstrate that NK cells can dramatically decrease the intensity and duration of pDC activation by controlling viral burden, which prevents the production of very high systemic levels of IFN-a/b, and eventually other innate cytokines, that can have detrimental effects for the host. We show that this mechanism also protects against the MCMV-mediated loss of splenic cDCs [36] . It has been reported that that both measles virus and LCMV can exploit the host's IFN-a/b response to inhibit cDC development and drive cDC loss in vivo [19] . Our results suggest that MCMV also can induce high production of IFN-a/b to promote its own survival by ablating cDCs and delaying the activation of antiviral effector CD8 T cells. In light of this observation, it is interesting to note that MCMV has developed strategies to actively counteract the antiviral responses to IFN-a/b or IFNc within infected cells [48] , as opposed to the mechanisms employed by negative-strand RNA viruses, which act to shut down the production of these cytokines by infected cells [49] or pDCs [50] . Indeed, even though complete deficiency in IFN-a/b responses is associated with a dramatic increase in the susceptibility of mice to MCMV infection [16] , it clearly appears that the benefit of high level IFN-a/b production for the host is less than that brought by an efficient NK cell response (since Klra8 mice show viral titers that are 1,000fold lower than those seen in BALB/c mice, even though Klra8 mice produce 100-fold less IFN-a/b). Thus, it is tempting to speculate that the efficient NK cell activity driven by the Ly49H activating receptor and its ability to dampen pDC IFN-a/b production and to promote adaptive immunity is a direct host countermeasure to the subversion of the IFN-a/b response by MCMV. Altogether, our results suggest that the NK cell response governs the balance between the positive and negative effects of IFN-a/b, and eventually other innate cytokines, for the optimal orchestration of the immune response to MCMV.