The various studies on pDCs in the context of infections by herpesviruses show a strong involvement of these cells in the antiviral immune response. Corresponding key issues are summarized in Table 3 . Both in vitro and in vivo, pDCs are the major source of IFN-I during stimulations or infections by herpesviruses. IFN-I responses have been shown to play a critical role in the control of these viral infections, in particular in the case of MCMV or HSV2. pDCs have a unique ability to rapidly produce high and systemic levels of IFN-I, without the requirement for endogenous viral replication, upon engulfment of viral products. This can be explained by the constitutive expression in pDCs of a specific set of viral sensors, including TLR7 and TLR9, and of downstream signaling molecules including MyD88 and IRF7, arranged as preassembled multimolecular complexes in special endosomes. Although the expression of some of these molecules can be shared with other immune cell subsets, this is not the case of the whole set altogether as a preassembled endosomal multimolecular complex. In addition, pDCs are also able to produce multiple other cytokines or chemokines upon activation by herpesviruses. Thus, pDCs are likely to play a non redundant role in the induction and regulation of innate immune responses to herpesviruses. It should be noted that humans with genetic deficiencies in signaling components known to be critical for pDC IFN-I production in response to viral stimulation do not appear to suffer from life threatening viral infections, except for herpes simplex encephalitis [171, 172] . This suggests that constitutive lack of pDC-derived IFN-I does not compromise the ultimate control of herpesvirus infections in humans in the absence of generalized immunodeficiency and in the context of the advanced health care system of developed countries. However, very recently, the sequencing and analysis of the ten human TLRs in over 150 individuals from various ethnicity demonstrated that the endosomal TLRs have evolved under strong purifying selection, including TLR7 and TLR9 which are selectively expressed to high levels in pDCs in humans. This suggests an essential non-redundant role of the endosomal TLRs in host survival "either via protective immunity against viral infections (present or past), or because of their additional involvement in other non immunity related processes of major biological relevance, or both" [173] . In any case, the possibility to harness pDC functions in the clinic to help treat infections with herpesviruses in immunocompromised individuals is promising. Topical treatments of genital lesions due to recurrent herpesvirus infections have indeed already given encouraging results. The role of pDCs in the regulation of adaptive immune responses to herpesvirus infections is less well understood. It is clear that pDCs can promote antiviral CD8 T cell responses through cDC instruction by soluble factors as well as cell-to-cell contacts. Whether pDCs bear a significant contribution to the direct priming of antiviral T lymphocytes in vivo during viral infections, as compared to cDCs, remains an open question on which future work will likely focus in the coming years. Moreover, pDCs are also able of inducing immunosuppression or tolerance under specific experimental conditions, which has not been yet studied in the context of infections with herpesviruses in vivo.