The CD8⁺ conventional dendritic cells (CD8 cDCs) and the plasmacytoid dendritic cells (pDC) are major producers of IFN-lambda (IL-28/29). Previously we have shown that upon stimulation with dsRNA the murine CD8 cDCs were the exclusive source of IFN-lambda in vivo and in vitro via a TLR3/TRIF dependent recognition pathway. A finding confirmed for the human equivalent cDCs expressing CD141 (BDCA3). In contrast, pDCs ignored dsRNA but produced large amounts of IFN-lambda in response to TLR7 or TLR9 stimuli in a MyD88 dependent way. Here we demonstrate that both, the CD8 cDCs and pDCs, are able to produce IFN-lambda in response to DNA viruses such as HSV-1 or poxviruses. Our analysis of the pattern recognition receptors or adaptor molecules involved revealed that pDCs mainly use TLR9 and MyD88 for the detection of the DNA viruses, whereas CD8 cDCs depend on the adaptor molecule STING but not on MyD88. The transfection of CD8 cDCs with different forms of dsDNA or cyclic-di-nucleotides such as c-di-GMP or c-GAMP induced, similar to the infection with DNA viruses, large amounts of IFN-lambda in a STING dependent way. Thus, the immune system produces IFN-lambda in response to DNA via two different DC subsets (CD8 cDCs and pDCs), different pattern recognition receptors (cytoplasmic DNA receptors and TLR9) and adaptor molecules (STING and MyD88) as well as downstream signalling components (IRF3 and IRF7). We hypothesize; that this widespread redundancy counteracts viral or other pathogen encoded inhibitory mechanisms, possibly acting on the specific DC subsets, the pattern recognition receptors and adaptor molecules or other signalling components.