| First Author | Trinath J | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 23 | Pages | 4301-14 |
| PubMed ID | 25246634 | Mgi Jnum | J:224325 |
| Mgi Id | MGI:5662025 | Doi | 10.1128/MCB.00641-14 |
| Citation | Trinath J, et al. (2014) The WNT signaling pathway contributes to dectin-1-dependent inhibition of Toll-like receptor-induced inflammatory signature. Mol Cell Biol 34(23):4301-14 |
| abstractText | Macrophages regulate cell fate decisions during microbial challenges by carefully titrating signaling events activated by innate receptors such as dectin-1 or Toll-like receptors (TLRs). Here, we demonstrate that dectin-1 activation robustly dampens TLR-induced proinflammatory signature in macrophages. Dectin-1 induced the stabilization of beta-catenin via spleen tyrosine kinase (Syk)-reactive oxygen species (ROS) signals, contributing to the expression of WNT5A. Subsequently, WNT5A-responsive protein inhibitors of activated STAT (PIAS-1) and suppressor of cytokine signaling 1 (SOCS-1) mediate the downregulation of IRAK-1, IRAK-4, and MyD88, resulting in decreased expression of interleukin 12 (IL-12), IL-1beta, and tumor necrosis factor alpha (TNF-alpha). In vivo activation of dectin-1 with pathogenic fungi or ligand resulted in an increased bacterial burden of Mycobacteria, Klebsiella, Staphylococcus, or Escherichia, with a concomitant decrease in TLR-triggered proinflammatory cytokines. All together, our study establishes a new role for dectin-1-responsive inhibitory mechanisms employed by virulent fungi to limit the proinflammatory environment of the host. |
