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.

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