Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17.
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.
LeibundGut-Landmann
Salomé
S
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK.
Gross
Olaf
O
Robinson
Matthew J
MJ
Osorio
Fabiola
F
Slack
Emma C
EC
Tsoni
S Vicky
SV
Schweighoffer
Edina
E
Tybulewicz
Victor
V
Brown
Gordon D
GD
Ruland
Jürgen
J
Reis e Sousa
Caetano
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D053468:CARD Signaling Adaptor Proteins; D002176:Candida albicans / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D000099181:Dectin-1
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D053468:CARD Signaling Adaptor Proteins; D020381:Interleukin-17; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D000099181:Dectin-1; C513280:Card9 protein, mouse; C000606897:Syk protein, mouse