According to published data, the CD11c + cell population contains different types of DCs, as well as other cells such as lymphocytes, macrophages, granulocytes and NK cells [51, 52, 53] . We therefore further separated the purified CD11c + cells into mDCs (CD11c + CD11b + Gr1 2 ), pDCs (CD11c + CD11b 2 GR1 + B220 + ) and a CD11c + CD11b-F4/80 + subpopulation ( Fig. S4A -D) and measured the expression of IFN-a, IFN-b and b-actin with real-time RT-PCR. After normalization to b-actin expression, we found that on a per cell basis mDCs expressed significantly more IFN-b than pDCs (Fig. 2D ), but both mDCs and pDCs expressed similar amounts of IFN-a (Fig. 2E ). In contrast, CD11c + , CD11b 2 cells carrying the macrophage marker F4/80 + did not express detectable amounts of IFN-a or IFN-b. Since mDCs comprise approximately 60% of all analyzed CD11c + splenocytes and their numbers are approximately 10-times higher than those of pDCs (Fig. S5A , B and [50] ), these results suggested that the vast majority of IFN-ab in Ad-infected mice was produced by splenic mDCs. To verify this assumption, we analyzed the Ad-elicited cytokine responses in mice depleted of CD11c high MHC II + myeloid DCs. To ablate these cells, we injected diphtheria toxin into the CD11c-diphtheria toxin receptor CD11cDTR/GFP transgenic mice [54] 24 h prior to infection with Ad. In agreement with previous reports [55, 56] , DT pre-treatment of DTR/GFP transgenic mice resulted in the ablation of CD11c high MHC II + CD11b + splenic mDCs, whereas the CD11c int Siglec H + CD11b 2 plasmacytoid DCs remained unaffected (Fig. S5A, B) . When DT pre-treated CD11cDTR/GFP transgenic mice were challenged with Ad3 and examined for IFN-ab in plasma 4 and 8 h after infection, only marginal IFN responses were found at both timepoints, in contrast to the strong responses of similarly infected transgenic control mice that had not received DT (Fig. 3A) . The same pretreatment with DT had no effect on the Ad elicited IFN-ab response of wild-type mice (Fig. 3A) .