Signal Transduction Pathways Activated by CpG-DNA

In the last few years, it has been shown that bacterial DNA stimulates and is recognized by cells of the immune system (Wagner 1999). Cell types that have been shown to respond directly to bacterial DNA include cells of the innate immune system, such as macrophages and dendritic cells, as well as B cells. Notably, the pattern of responsive cell types strongly resembles the pattern of cells stimulated by other so-called pattern-recognition factors, such as lipopolysaccharides (LPS). In addition, the spectrum of effects induced by these biochemically different agents are remarkably similar to each other. It includes induction of a variety of soluble factors, upregulation of membrane proteins and regulation of cell proliferation and survival. Due to the profound alterations in the cells' behaviour upon stimulation by CpG-DNA, it has been compelling to postulate changes in the transcriptional and post-transcriptional activities. How can the information contained in unmethylated CpG-motifs in bacterial DNA be translated into gene expression? One possibility is that CpG-DNA, like other common ligands, engages a specific cellular receptor that transduces the signal by signal transduction pathways from the outside to the nucleus. Recently, it was shown that classic signal transduction pathways, such as the stress-kinase pathway and the nuclear factor ĸB (NF-ĸB) activation pathway, are switched on in response to CpG-DNA. The current knowledge about these pathways in the context of their activation by CpG-DNA and the upstream requirements for signal initiation are discussed in this chapter.