IRF7 is the master transcription factor controling IFN-I production in response to viral type stimuli, as IRF7 -/mice show dramatic decreases in IFN-I production and enhanced mortality in response to challenges with different viruses, including MCMV [52] or HSV-1 [92] . Human and mouse pDCs constitutively express very high levels of IRF7 [80] . In contrast, in cDCs and other cell types, IRF7 expression is induced only secondarily to a first, IRF3-dependent, wave of IFN-β/α4 production [93] but is critical to drive the consecutive production of the other IFN-α suptypes in a positive feedback loop. Loss of IRF7 expression abolishes pDC responses to MCMV [52], HSV-1 and all the other viral stimuli that have been tested [92] . Thus, high constitutive expression of IRF7 strongly contributes to the unique ability of pDCs to produce high level of all IFN-I subtypes very rapidly upon viral stimulation. In addition, as compared to cDCs, pDCs are characterized by a long retention time of CpG desoxyoligonucleotides in dedicated, transferrin receptor + , endosomes where preformed multimolecular complexes exist which bridge together TLR7/9 and their downstream signaling machinery including MyD88 and IRF7 [94, 95] .