We also tested whether IFN-abR-dependent signaling is involved in the IFN-ab response of Ad-infected BMDCs in vitro. As with the in vivo results, we found that cells from IFN-abR 2/2 mice infected with Ad3 produced significantly less type I IFN than similarly infected cells from wt mice (Fig. S8 ). The loss of IFN-ab signaling also resulted in a strong inhibition of the Ad induced IL-6 production in BMDCs (Fig. 5D ) and BMMs (Fig. 5E ). Furthermore, as shown using Ad-infected BMMs, it resulted also in a strong reduction of inducibility of IL-6 mRNA expression (Fig. 5F ). Because transcriptional changes are often determined by epigenetic factors [62] we checked the levels of hyperacetylated histone H4 (acH4), a permissive factor for transcription at the IL-6 promoter in control and Ad-infected BMMs from wt and IFNabR 2/2 mice. Chromatin immunoprecipitation (ChIP) assays showed a significant enrichment of acH4 at the IL-6 promoter in infected wt, but not IFNabR 2/2 BMMs (Fig. 5G) . In a control experiment, as expected, an enrichment of acH4 was observed at the promoter of the constitutively active Topoisomerase 3b but not of the l5 (not expressing, active only in early B-cells) gene in both cells types. From these results we conclude that IFN-ab exerts a positive regulatory effect on the Ad-induced IL-6 transcription and that its loss is at least partly responsible for the strong reduction of the IL-6 response in Ad-infected IFN-abR knockout mice.