TY - JOUR
T1 - Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins
AU - Rogers, Neil C.
AU - Slack, Emma C.
AU - Edwards, Alexander D.
AU - Nolte, Martijn A.
AU - Schulz, Oliver
AU - Schweighoffer, Edina
AU - Williams, David L.
AU - Gordon, Siamon
AU - Tybulewicz, Victor L.
AU - Brown, Gordon D.
AU - Reis e Sousa, Caetano
PY - 2005
Y1 - 2005
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.immuni.2005.03.004
DO - https://doi.org/10.1016/j.immuni.2005.03.004
M3 - Article
C2 - 15845454
SN - 1074-7613
VL - 22
SP - 507
EP - 517
JO - Immunity
JF - Immunity
IS - 4
ER -