Abstract
Dendritic cells (DC) are instrumental in handling pathogens for processing and presentation to T cells, thus eliciting an appropriate immune response. C-type lectins expressed by DC function as pathogen-recognition receptors; yet their specificity for carbohydrate structures on pathogens is not fully understood. In this study, we analyzed the carbohydrate specificity of DC-specific ICAM-3-grabbing nonintegrin (SIGN)/CD209, the recently documented HIV-1 receptor on DC. Our studies show that DC-SIGN binds with high affinity to both synthetic mannose- and fucose-containing glycoconjugates. These carbohydrate structures are abundantly expressed by pathogens as demonstrated by the affinity of DC-SIGN for natural surface glycans of the human pathogens Mycobacterium tuberculosis, Helicobacter pylori, Leishmania mexicana, and Schistosoma mansoni. This analysis expands our knowledge on the carbohydrate and pathogen-specificity of DC-SIGN and identifies this lectin to be central in pathogen-DC interactions.
MeSH terms
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Animals
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CHO Cells
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Carbohydrate Metabolism*
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Carbohydrate Sequence
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Carbohydrates / immunology*
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Cell Adhesion / immunology
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cells, Cultured
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Cricetinae
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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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Dendritic Cells / parasitology*
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Fucose / immunology
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Fucose / metabolism
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Helicobacter pylori / immunology
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Helicobacter pylori / pathogenicity
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Humans
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K562 Cells
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism*
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Leishmania mexicana / immunology
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Leishmania mexicana / pathogenicity
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Mannose / immunology
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Mannose / metabolism
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Molecular Sequence Data
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Mycobacterium tuberculosis / immunology
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Mycobacterium tuberculosis / pathogenicity
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Protein Binding / immunology
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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Schistosoma mansoni / immunology
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Schistosoma mansoni / pathogenicity
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Transfection
Substances
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Carbohydrates
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Lectins, C-Type
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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Fucose
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Mannose