In humans, several case reports have been published describing patients suffering from severe herpesvirus infections associated with decreased numbers of circulating pDCs as compared to healthy controls and with an impaired IFN-I production ability as assessed by in vitro restimulation of their PBMCs with the virus [54-56]. EBV infection of humanized NOD-SCID mice was reported to lead to a decrease in the numbers of circulating pDCs and in the ability of PBMCs to produce IFN-I upon in vitro restimulation [11] . This raises the question of whether the pDC deficiency reported in certain patients with severe herpesvirus infections could be a consequence rather than a cause of the disease. In any case, interestingly, reconstitution of NOD-SCID mice with pDC-enriched human PBMCs delayed their mortality upon consecutive infection with EBV [11] . It has been recently shown that chronic infection of mice with LCMV causes a long-lasting impairment of pDC ability to produce IFN-I upon activation with viral type stimuli and enhances sensitivity to a secondary unrelated infection with MCMV [57]. Thus, it has been proposed that enhanced sensitivity to opportunistic viruses in patients with human immunodeficiency type 1 (HIV-1) infection could in part result from decreased pDC responsiveness [57, 58] . A recent study indeed shows that while IFN-I can be detected in the spleens of patients with chronic HIV-1 infection, pDCs appear to make only a very low contribution to this function [59] In this regard, it is striking that herpesviruses are amongst the most common opportunistic agents causing life-threatening disease in HIV-1-infected infants [60] or in AIDS patients [61,62] who have a dramatic reduction in pDC numbers and an impairment of pDC functions [63] in addition to the deregulation of many other immune functions. Reactivation of latent infections with herpesviruses, in particular HCMV, is also a major cause of morbidity and mortality in bone marrow or solid organ transplantation recipients [64] , who undergo immunosuppressive treatments known to profoundly affect pDC numbers or functions [65] [66] [67] .