The ''classical'' cytosolic pathway is the major IFN-ab producing mechanism in cells other than pDCs [22, 23] . Signal transduction leading to type I IFN gene induction is initiated by the recognition of intracellular virus-associated molecular patterns. dsRNA and 59-triphosphate RNA produced during viral replication are sensed by the RNA helicases RIG-I and MDA-5 [23, 24, 25, 26, 27, 28] . This pathway has been extensively studied, mainly in virus-infected fibroblasts. Triggering of the aforementioned RNA helicases leads to the activation of the transcription factors NF-kB, IRF-3 and IRF-7 that are important for the induction of IFN-ab and proinflammatory cytokines, including IL-6. In the cytosolic pathway, type I IFN gene induction is a sequential event and both IRF-3 and IRF-7 were shown to be important in the early phase when mostly IFN-b is produced. The late phase of the IFN-ab response is regulated by positive feedback via the increased levels of IRF-7 elicited by IFN-b production during the early phase [29, 30, 31] . In addition to fibroblasts, the potential of mDCs and macrophages to produce significant amounts of type I IFNs in response to viral replication has been demonstrated in vitro [32, 33] ; however, in vivo the specific contribution of these cells to systemic levels of IFN-ab is not well documented.