Abstract
The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1-Syk-CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (T(H)-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent T(H)-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of T(H)-17 responses to some pathogens.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism*
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Adjuvants, Immunologic
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Animals
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Antibody Formation / immunology
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CARD Signaling Adaptor Proteins
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Candida albicans / immunology
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Cell Differentiation
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Cells, Cultured
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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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Immunity, Innate / immunology*
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Interleukin-17 / biosynthesis*
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Intracellular Signaling Peptides and Proteins / metabolism*
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Lectins, C-Type
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Membrane Proteins / agonists
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / agonists
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Protein-Tyrosine Kinases / metabolism*
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Signal Transduction
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Syk Kinase
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic
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CARD Signaling Adaptor Proteins
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Card9 protein, mouse
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Interleukin-17
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Intracellular Signaling Peptides and Proteins
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Lectins, C-Type
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Membrane Proteins
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Nerve Tissue Proteins
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dectin 1
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse