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

NC Rogers, EC Slack, AD Edwards, MA Nolte… - Immunity, 2005 - cell.com
NC Rogers, EC Slack, AD Edwards, MA Nolte, O Schulz, E Schweighoffer, DL Williams
Immunity, 2005cell.com
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 β-glucan receptor Dectin-1, a yeast binding C type lectin known to
synergize with TLR2 to induce TNFα and IL-12, can also promote synthesis of IL-2 and IL-10 …
Summary
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 β-glucan receptor Dectin-1, a yeast binding C type lectin known to synergize with TLR2 to induce TNFα 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.
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