Figure 1. Type I IFN production pathways in human pDC and cDC/mDC.
pDC utilize a variety of cell-surface receptors to endocytose viruses into endosomes where the viral nucleic acid is uncoated. There, the RNA or DNA interacts with TLR7 and -9, respectively, to induce type I IFN gene expression independent of viral replication and in a MyD88-dependent manner. pDC express high constitutive levels of the transcription factor, IRF-7 that is required for the induction of IFN-α. cDC also utilize a TLR-dependent pathway for the sensing of viral RNA – TLR3, which recognizes dsRNA within the endosomes. This IFN response, however, requires autocrine IFN feedback to upregulate IRF-7 expression to get the full range of IFN subtype expression. In addition to the TLR-dendent IFN induction, both types of DC have MyD88 independent mechanisms for recognition of cytoplasmic viruses following infection of the cells with virus, including the RIG-I system for recognition of cytoplasmic dsRNA and an as yet undefined cytoplasmic sensor for DNA.