Abstract
TLR9 recognizes DNA sequences containing hypomethylated CpG motifs and is a component of the innate immune system highly conserved during eukaryotic evolution. Previous reports suggested that the expression of TLR9 is restricted to plasmacytoid dendritic cells and B lymphocytes. Our results indicate that low levels of TLR9 are present on the cell surface of freshly isolated human monocytes, and expression is greatly increased by infection with Yersinia pestis. Enhanced cell surface TLR9 coincided with elevated levels of cytoplasmic TLR9 and recruitment of MyD88. Infected monocytes differentiated into mature dendritic cells, expressed IFN-alpha, and stimulated proliferative and cytotoxic T cell responses specific to Y. pestis. Furthermore, uninfected B cells and monocytes both increased cell surface TLR9, CD86, and HLA-DR in response to treatment with CpG-containing oligonucleotides, whereas cell surface TLR9 was down-modulated on infected dendritic cells by the addition of agonist oligonucleotide. Our results suggest that increased expression of TLR9 on the surface of infected cells may serve a role as an activation signal to other cells of the immune system.
MeSH terms
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Antigen Presentation / immunology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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B-Lymphocyte Subsets / microbiology
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Bacterial Proteins / immunology
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Cell Differentiation / immunology
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cell Separation
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Cells, Cultured
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Cytotoxicity Tests, Immunologic
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / biosynthesis*
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / microbiology*
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Dose-Response Relationship, Immunologic
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Down-Regulation / immunology
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Humans
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Lipopolysaccharide Receptors / biosynthesis
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Lymphocyte Activation / immunology
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Monocytes / cytology
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Monocytes / immunology*
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Monocytes / metabolism
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Monocytes / microbiology*
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Oligodeoxyribonucleotides / pharmacology
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Receptors, Cell Surface / agonists
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / biosynthesis*
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T-Lymphocytes, Cytotoxic / immunology
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Toll-Like Receptor 9
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Up-Regulation / immunology
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Yersinia pestis / immunology*
Substances
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Bacterial Proteins
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CPG-oligonucleotide
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DNA-Binding Proteins
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Lipopolysaccharide Receptors
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Oligodeoxyribonucleotides
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Receptors, Cell Surface
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TLR9 protein, human
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Toll-Like Receptor 9
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caf1 protein, Yersinia pestis