title: Mechanisms of TLR9 activation.
abstract: Non-methylated CpG-motifs in bacterial or viral DNA are recognized by TLR9 as foreign. The activation of TLR9 by microbial DNA or synthetic oligonucleotides based on these motifs leads to the induction of innate immune responses. We have compared the subcellular localization of fluorescent versions of TLR9 and TLR4 and found that TLR9 is expressed in the endoplasmic reticulum while TLR4 is expressed on the plasma membrane. Fluorescently tagged bacterial DNA or CpG-DNA was observed to traffic to a tubular lysosomal compartment in human pDCs. In stimulated cells, TLR9 translocated to CpG-DNA or microbial DNA containing structures in the endosome, where TLR9 binds to DNA and initiates signaling.
authors.affiliation: Division of Infectious Diseases, University of Massachusetts Medical School, 364 Plantation Street, LRB 370M, Worcester, MA 01605, USA. eicke.latz@umassmed.edu
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.forename: Alberto
authors.initials: A
authors.lastname: Visintin
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
mesh_terms: D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D004269:DNA, Bacterial / Q000235:genetics / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008247:Lysosomes / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D018613:Microscopy, Confocal; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
chemical_list: D004269:DNA, Bacterial; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors