Taken together these data highlight the primordial role of pDCs as major IFN-I producers in response to systemic or local herpesvirus infections in vivo. However, this phenomenon cannot be generalized to all viruses as pDCs are not the major producers of IFN-I with certain viruses such as lymphocytic choriomeningitis virus (LCMV) [12] or upon local infections of the airways such as with intranasal Newcastle disease virus (NDV) [47] or influenza [48, 49] challenges. During reovirus infections, cDCs contribute as well as pDCs to IFN-I production locally in the intestine [50] . It is noteworthy that we could not detect any IFN-I production by pDCs from the blood, lymph nodes, liver or lung of MCMV-infected mice, despite high levels of viral replication in some of these organs [43] . This is consistent with a similar observation reported by the group of Shizuo Akira in the intravenous NDV infection model [47] . This suggests that splenic pDCs are especially prone to high level IFN-I production upon systemic acute viral infections as opposed to pDCs located in some other organs such as the liver or the lung. The mechanisms for this differential responsiveness to viral stimuli of pDCs from distinct tissues are not clear, although a role of the local cytokine milieu has been proposed [51].