title: Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection.
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.
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, England, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Robinson
authors.forename: Fabiola
authors.initials: F
authors.lastname: Osorio
authors.forename: Marcela
authors.initials: M
authors.lastname: Rosas
authors.forename: Rui P
authors.initials: RP
authors.lastname: Freitas
authors.forename: Edina
authors.initials: E
authors.lastname: Schweighoffer
authors.forename: Olaf
authors.initials: O
authors.lastname: Gross
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
authors.forename: Victor
authors.initials: V
authors.lastname: Tybulewicz
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Luis Ferreira
authors.initials: LF
authors.lastname: Moita
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002177:Candidiasis / Q000276:immunology*; D005434:Flow Cytometry; D015151:Immunoblotting; D020381:Interleukin-17 / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D053468:CARD Signaling Adaptor Proteins; D020381:Interleukin-17; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D053594:Myeloid Differentiation Factor 88; D011505:Protein-Tyrosine Kinases; D051192:Receptors, Pattern Recognition; D000072377:Syk Kinase; C513280:Card9 protein, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C445340:dectin-2, mouse; C000606897:Syk protein, mouse
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