In summary, manipulation of pDC numbers or functions in mice and epidemiological analyses in humans strongly suggest that high level production of IFN-I by pDCs contributes to the control of infections by herpesviruses. However, its importance could vary significantly between individuals depending on their capacity to concomitantly mount other immune responses redundant for this function. There is currently no experimental system available to the scientific community that allows the disruption of pDC functions in vivo in an entirely specific and completely efficient way. The genetic engineering of mouse models designed to fill this need should be seen as a priority in this research field, because this will be the only rigorous way to evaluate the role of pDCs in vivo in the defense against herpesviruses and more generally in the orchestration of the immune responses to viral infections. The recent demonstration that the conditional knockout of the transcription factor TCF4 (also referred to as E2-2) in adult mice leads to a complete and selective loss of pDCs constitutes a significant advance towards this goal [68] .