Abstract
Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of immune responses to infection. Studies with Dectin-1, a PRR for fungi, have defined a novel innate signaling pathway involving Syk kinase and the adaptor CARD9, which is critical for inducing Th17 responses to fungal infection. We show that another C-type lectin, Dectin-2, also signals via Syk and CARD9, and contributes to dendritic cell (DC) activation by fungal particles. Unlike Dectin-1, Dectin-2 couples to Syk indirectly, through association with the FcRgamma chain. In a model of Candida albicans infection, blockade of Dectin-2 did not affect innate immune resistance but abrogated Candida-specific T cell production of IL-17 and, in combination with the absence of Dectin-1, decreased Th1 responses to the organism. Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk-CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / immunology
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Adaptor Proteins, Signal Transducing / metabolism
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Adaptor Proteins, Vesicular Transport / genetics
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Animals
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CARD Signaling Adaptor Proteins
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Candidiasis / immunology*
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Flow Cytometry
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Immunoblotting
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Interleukin-17 / immunology
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Intracellular Signaling Peptides and Proteins / immunology*
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Intracellular Signaling Peptides and Proteins / metabolism
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Lectins, C-Type / immunology*
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Lectins, C-Type / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Differentiation Factor 88 / genetics
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Protein-Tyrosine Kinases / immunology*
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Protein-Tyrosine Kinases / metabolism
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Receptors, Pattern Recognition / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / immunology*
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Syk Kinase
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T-Lymphocytes, Helper-Inducer / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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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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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Pattern Recognition
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TICAM-1 protein, mouse
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dectin-2, mouse
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse