In mice, boosting pDC responses has also been shown to enhance resistance to systemic infection with MCMV or HSV-1. This has been achieved either through the systemic administration of the Thymosin-α1 peptide [41] or of FLT3L [162] . In both cases, enhanced protection against the viral infection resulted from increased IFN-I or IL-12 production. For the MCMV infection, this was shown to depend on the activation of the TLR9/MyD88/IRF7 pathway in pDCs and to lead to a higher NK cell activation. Since a deficiency in pDC responses has been proposed to be implicated in the susceptibility of bone marrow or solid organ transplant recipients to HCMV reactivation or primary infection [65, 67] , therapeutic strategies aimed at restoring normal pDC functions in this physiopathological context may bring clinical benefits (Scheme 2). However, as compared to the local activation of pDCs in skin or mucosa by topical application of TLR agonists, systemic activation of pDCs may bear increased risks of detrimental side effects. Thus, further studies will be required to determine the best strategy to harness pDCs for the promotion of efficient systemic innate antiviral defenses without triggering excessive inflammation and consecutive immunopathology. Scheme 2. Impact of the fine tuning of pDC activation on the promotion of health versus disease. During herpesvirus infections, disease can result either from immune failure to control viral replication early or from the development of immunopathology. Weak pDC activation could contribute to disease in the former case, and excessive pDC activation in the latter case. Immunopathology can cause immune-mediated damage to vital organs and/or compromise the ability of adaptive immunity to control viral replication later. Thus, a significant but controlled pDC activation is required to promote health over disease, by allowing early control of viral replication while not causing significant immunopathology. Therapeutic protocols aimed at boosting or dampening pDC responses could thus help to reach this balance and to fight disease under defined clinical conditions, as discussed in the body of this review.