Although TLR9/MyD88-independent IFN-I synthesis has also been observed in mice infected with viruses [40]–[42], several reports suggest that the engagement of the pDC/TLR system for IFN-I production occurs when viruses gain access to lymphoid tissue either directly or because the pathogen breaks the initial barrier of infection formed by macrophages and/or epithelial cells [34], [41]–[43]. Here, MYD88 is linked to infection.