Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection.
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.
Robinson
Matthew J
MJ
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, England, UK.
Osorio
Fabiola
F
Rosas
Marcela
M
Freitas
Rui P
RP
Schweighoffer
Edina
E
Gross
Olaf
O
Verbeek
J Sjef
JS
Ruland
Jürgen
J
Tybulewicz
Victor
V
Brown
Gordon D
GD
Moita
Luis Ferreira
LF
Taylor
Philip R
PR
Reis e Sousa
Caetano
C
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*
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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