Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins.
Pattern-recognition receptors (PRRs) detect molecular signatures of microbes and initiate immune responses to infection. Prototypical PRRs such as Toll-like receptors (TLRs) signal via a conserved pathway to induce innate response genes. In contrast, the signaling pathways engaged by other classes of putative PRRs remain ill defined. Here, we demonstrate that the beta-glucan receptor Dectin-1, a yeast binding C type lectin known to synergize with TLR2 to induce TNF alpha and IL-12, can also promote synthesis of IL-2 and IL-10 through phosphorylation of the membrane proximal tyrosine in the cytoplasmic domain and recruitment of Syk kinase. syk-/- dendritic cells (DCs) do not make IL-10 or IL-2 upon yeast stimulation but produce IL-12, indicating that the Dectin-1/Syk and Dectin-1/TLR2 pathways can operate independently. These results identify a novel signaling pathway involved in pattern recognition by C type lectins and suggest a potential role for Syk kinase in regulation of innate immunity.
Rogers
Neil C
NC
Immunobiology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Slack
Emma C
EC
Edwards
Alexander D
AD
Nolte
Martijn A
MA
Schulz
Oliver
O
Schweighoffer
Edina
E
Williams
David L
DL
Gordon
Siamon
S
Tybulewicz
Victor L
VL
Brown
Gordon D
GD
Reis e Sousa
Caetano
C
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology; D004792:Enzyme Precursors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D015054:Zymosan / Q000494:pharmacology; D047071:beta-Glucans / Q000378:metabolism; D000099181:Dectin-1
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D011971:Receptors, Immunologic; D000072377:Syk Kinase; D015054:Zymosan; D047071:beta-Glucans; D000099181:Dectin-1; C507780:Myd88 protein, mouse; C000606897:Syk protein, mouse