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Due to the importance of foreign- and host-derived DNA for induction of protective reactions against pathogens and autoimmune disorders, respectively, a great deal of research has been devoted to studying the immunostimulatory properties of CpGs and the function of TLR9 (reviewed in [7]). In mammals, the receptor is found in the endoplasmic reticulum in resting immune cells. Upon exposure of the cells to CpG DNA, TLR9 translocates to the endosomal compartments [8], where it may interact with its ligand. The binding of the receptor to DNA seems to be sequence independent but it requires low pH conditions and proteolytical activation [9]. Once activated, the receptor signals through Myeloid differentiation primary response gene 88 (MyD88) to activate transcription factors including nuclear factor kappa-B (NFkB) and interferon-regulatory factor 7 (IRF7) involved in the upregulation of proinflammatory genes and type I interferon (IFN), respectively.
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