Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity.
The astounding adjuvanticity and Th1-polarizing immunobiology of bacterial CpG-DNA and mimicking CpG-oligonucleotides continue to mirror promising therapeutic potential. The past year has witnessed some particularly impressive progress in knowledge of its molecular mode of action. Accordingly, CpG-DNA acts as a "pathogen-associated" molecular pattern that is recognized by TLR9 expressed, in particular, by dendritic cells. Interactions between CpG-DNA and TLR9 rapidly activate antigen-presenting dendritic cells through the ancient Toll/IL-1-receptor signaling pathway to upregulate co-stimulatory molecules and to produce Th1-polarizing cytokines, such as interleukin-12 and interleukin-18. Thus, interactions between CpG-DNA and TLR9 effectively bridge innate and acquired immunity.
Wagner
Hermann
H
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Trogerstrasse 9, 81675 Munich, Germany. h.wagner@lrz.tu-muenchen.de
D000818:Animals; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism; D018899:CpG Islands / Q000502:physiology*; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D029721:Drosophila Proteins; D015870:Gene Expression; D006801:Humans; D007110:Immunity, Active / Q000502:physiology*; D007113:Immunity, Innate / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors