Abstract
Bacterial DNA contains CpG oligonucleotide (ODN) motifs to trigger innate immune responses through the endosomal receptor Toll-like receptor 9 (TLR9). One of the cell surface receptors to capture and deliver microbial DNA to intracellular TLR9 is the C-type lectin molecule DEC-205 through its N-terminal C-type lectin-like domain (CTLD). CD93 is a cell surface protein and member of the lectin group XIV with a CTLD. We hypothesized that CD93 could interact with CpG motifs, and possibly serve as a novel receptor to deliver bacterial DNA to endosomal TLR9. Using ELISA and tryptophan fluorescence binding studies we observed that the soluble histidine-tagged CD93-CTLD was specifically binding to CpG ODN and bacterial DNA. Moreover, we found that CpG ODN could bind to CD93-expressing IMR32 neuroblastoma cells and induced more robust interleukin-6 secretion when compared with mock-transfected IMR32 control cells. Our data argue for a possible contribution of CD93 to control cell responsiveness to bacterial DNA in a manner reminiscent of DEC-205. We postulate that CD93 may act as a receptor at plasma membrane for DNA or CpG ODN and to grant delivery to endosomal TLR9.
Keywords:
C-type lectin-like domain; CD93; CpG oligonucleotide; Toll-like receptor 9; bacterial DNA; inflammation.
© 2019 John Wiley & Sons Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / genetics
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Antigens, CD / immunology
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Biological Transport / genetics
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Biological Transport / immunology
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Cell Line, Tumor
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Cloning, Molecular
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DNA, Bacterial / genetics
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DNA, Bacterial / immunology*
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DNA, Bacterial / metabolism
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Endosomes / immunology
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Endosomes / metabolism
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Escherichia coli / chemistry
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Gene Expression Regulation / immunology*
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Humans
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Inflammation
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism
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Minor Histocompatibility Antigens / genetics
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Minor Histocompatibility Antigens / immunology
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Models, Biological
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Neurons / immunology
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Neurons / metabolism
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Neurons / pathology
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Oligodeoxyribonucleotides / genetics
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Oligodeoxyribonucleotides / immunology*
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Oligodeoxyribonucleotides / metabolism
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Protein Binding
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Protein Domains
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Complement / genetics
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Receptors, Complement / immunology*
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Receptors, Complement / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / immunology*
Substances
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Antigens, CD
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CPG-oligonucleotide
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DEC-205 receptor
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DNA, Bacterial
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IL6 protein, human
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Interleukin-6
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Lectins, C-Type
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Membrane Glycoproteins
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Minor Histocompatibility Antigens
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Oligodeoxyribonucleotides
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Receptors, Cell Surface
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Receptors, Complement
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Recombinant Fusion Proteins
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TLR9 protein, human
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Toll-Like Receptor 9
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complement 1q receptor