IFN-I were the first cytokines discovered, a little over 50 years ago, based on their direct, potent and broad antiviral activity [14, 15] . More generally, IFN-I are now known to play an essential role in the global orchestration of antiviral immunity, by linking innate and adaptive immunity through multiple immunoregulatory functions [16] . For instance, IFN-I do not only play a crucial role in the control of the replication of many viruses, but they can also promote NK cell or CD8 T cell antiviral cytotoxic activity, either directly [17] [18] [19] [20] or through the licensing of accessory cells such as conventional dendritic cells (cDCs) [13, [21] [22] [23] [24] . In mammals, there are one IFN-β and more than ten different IFN-α, the exact number of which varies across species. All of these IFN-I exert their activities by engaging an ubiquitous receptor (IFNAR) composed of two chains (IFNAR1 and IFNAR2) [25] . Although any cell type could theoretically produce IFN-I (at least IFN-β) when infected by a virus, one cell type specialized in the production of high levels of multiple species of IFN-I in response to herpesviruses and many other viruses has been identified and characterized in the last decade. It has been named IFN-I producing cells (IPCs) or plasmacytoid dendritic cells (pDCs). [5, 6, 7] No (blood pDCs) [6] Yes (tonsil pDCs) [7] Partial [8] Human [12] No ± [13] Yes ± [13] * pDCs have been described to be the main IFN-I source upon herpesvirus stimulation. ± including in vivo in mice $ maturation of pDCs following stimulation with herpesviruses in terms of CD40, CD80, CD86 and MHCII up-regulation ND: not determined In humans, pDCs are characterized by selective high level expression of the C-type lectin CLEC4C (also referred to as BDCA2) and of the immunoglobulin superfamily member LILRA4 (also referred to as ILT7). In mice, there are no orthologs of CLEC4C or LILRA4. Instead, mouse pDCs selectively express high levels of the C-type lectin SIGLECH and of the bone marrow stromal cell antigen 2 (BST2/CD317) membrane marker. SIGLECH is also found on a subset of marginal zone macrophages in the spleen. BST2 is induced at low to intermediate levels on a variety of immune cell types upon stimulation with IFN-I, including cDCs, and is also constitutively expressed on plasma cells. Therefore, mouse pDCs can be rigorously identified as CD11c int BST2 high or as CD11b -SIGLECH + . Although it has been frequently used, it is important to be aware that the combined expression of B220 and CD11c is not adequate to identify mouse pDCs, as B220 + CD11c + cells also encompass other leukocyte populations including a subset of NK cells [26] [27] [28] [29] and a precursor of cDCs [30] . While mouse and human pDCs are identified by different markers, they share many functional characteristics [31] and selective expression of over 200 genes as compared to other leukocyte subsets [28] . Thus, there clearly is a very strong homology between mouse and human pDCs, such that the investigation of the functions of pDCs in vivo in the mouse model should be largely relevant for understanding their biology in humans. The initial discovery and the functional study of pDCs have been closely linked to the study of innate immune recognition of herpesviruses. Indeed, together with the influenza virus [32-34], herpes simplex viruses were the very first viruses used to identify human [2] or mouse [35] pDCs in vitro, based on the much older observation that a rare cell type had the unique ability to rapidly recognize herpesviruses for consecutive high level production of IFN-I [36, 37] . We reported the first evidence that pDCs actually constitute the major source of systemic IFN-I production during a viral infection in vivo using MCMV as a model [12, 32] . To the best of our knowledge, pDCs have been shown able to recognize, and respond to, all of the herpesviruses tested (Table 1 ). These observations suggest that pDCs may be amongst the earliest sentinels for detection of, and defense against, herpesvirus infections. The present work aims at reviewing the current knowledge regarding the role of pDCs in the orchestration of the immune responses against herpesviruses, not only focusing on their beneficial role for the host but also raising the question of their possible implications in immunopathology under defined conditions, leading to the discussion of whether and how pDC responses to herpesviruses could be used in antiviral immunotherapy or vaccination.