Abstract
Several classes of CpG oligodeoxynucleotides (ODNs) with different immune stimulatory profiles were recently identified: the A-, B- and C-classes. In this study, we investigated the CpG-dependent stimulation of IFN-gamma-inducible protein 10 (IP-10 or CXCL10) in different human immune cell types. CpG ODNs induced IP-10 in monocytes, pDCs and in B cells. Purified B cells as well as RPMI 8226 cells responded to CpG stimulation by IP-10 production. Treatment with exogenous IFN-alpha2b sensitized PBMCs, purified B cells as well as RPMI 8226 cells to respond more efficiently to stimulation with CpG ODNs by IP-10 production. IP-10 signaling could be directly stimulated via TLR9 in CpG-unresponsive HEK293 cells transfected with human TLR9 and an IP-10 reporter construct. Therefore, CpG-mediated IP-10 production is stimulated through IFN-alpha in cells that express the IFN-alpha receptor, a second pathway for IP-10 induction exists in TLR9-expressing B cells and pDCs where IP-10 is stimulated directly upon CpG-mediated TLR9 signaling. Our data provide a better understanding of the mechanisms through which CpG ODNs induce efficient Th1 responses.
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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B-Lymphocytes / drug effects*
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B-Lymphocytes / immunology
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Cells, Cultured
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Chemokine CXCL10
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Chemokines, CXC / biosynthesis*
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CpG Islands / immunology*
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DNA Primers / chemistry
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dose-Response Relationship, Drug
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Humans
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Interferon alpha-2
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Interferon-alpha / pharmacology
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Interferon-gamma / pharmacology
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Kidney / drug effects
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Kidney / metabolism
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / immunology
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Membrane Glycoproteins / metabolism
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Monocytes / drug effects
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Monocytes / immunology
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Oligodeoxyribonucleotides / classification
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Oligodeoxyribonucleotides / pharmacology*
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Receptor, Interferon alpha-beta
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Receptors, Cell Surface / metabolism
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Receptors, Interferon / metabolism
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Recombinant Proteins
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Toll-Like Receptor 9
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Toll-Like Receptors
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Transfection
Substances
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Adjuvants, Immunologic
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CPG-oligonucleotide
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CXCL10 protein, human
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Chemokine CXCL10
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Chemokines, CXC
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DNA Primers
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Interferon alpha-2
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Interferon-alpha
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Membrane Glycoproteins
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Oligodeoxyribonucleotides
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Receptors, Cell Surface
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Receptors, Interferon
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Recombinant Proteins
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TLR9 protein, human
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Toll-Like Receptor 9
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Toll-Like Receptors
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Receptor, Interferon alpha-beta
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Interferon-gamma