Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins

Neil C Rogers; Emma C Slack; Alexander D Edwards; Martijn A Nolte; Oliver Schulz; Edina Schweighoffer; David L Williams; Siamon Gordon; Victor L Tybulewicz; Gordon D Brown; Caetano Reis e Sousa

doi:10.1016/j.immuni.2005.03.004

Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins

Immunity. 2005 Apr;22(4):507-17. doi: 10.1016/j.immuni.2005.03.004.

Authors

Neil C Rogers¹, Emma C Slack, Alexander D Edwards, Martijn A Nolte, Oliver Schulz, Edina Schweighoffer, David L Williams, Siamon Gordon, Victor L Tybulewicz, Gordon D Brown, Caetano Reis e Sousa

Affiliation

¹ Immunobiology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.

PMID: 15845454
DOI: 10.1016/j.immuni.2005.03.004

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
Antigens, Differentiation / metabolism
Cytokines / biosynthesis*
Dendritic Cells / immunology
Enzyme Precursors / metabolism*
Intracellular Signaling Peptides and Proteins
Lectins, C-Type / metabolism*
Membrane Proteins / metabolism*
Mice
Molecular Sequence Data
Myeloid Differentiation Factor 88
Nerve Tissue Proteins / metabolism*
Phosphorylation
Protein-Tyrosine Kinases / metabolism*
Receptors, Immunologic / metabolism
Signal Transduction*
Syk Kinase
Zymosan / pharmacology
beta-Glucans / metabolism

Substances

Adaptor Proteins, Signal Transducing
Antigens, Differentiation
Cytokines
Enzyme Precursors
Intracellular Signaling Peptides and Proteins
Lectins, C-Type
Membrane Proteins
Myd88 protein, mouse
Myeloid Differentiation Factor 88
Nerve Tissue Proteins
Receptors, Immunologic
beta-Glucans
dectin 1
Zymosan
Protein-Tyrosine Kinases
Syk Kinase
Syk protein, mouse