MiR-146a negatively regulates dectin-1-induced inflammatory responses

Dectin-1 is the critical sensor for beta-glucan from Candida which is the most common human fungal pathogen and cause superficial and system infection. MicroRNAs (miRNAs) play crucial roles in regulating innate immunity. However, the functional role of miRNAs in inflammatory response dependent on the activation of dectin-1 pathway has not been defined. In the present study, we found insoluble beta-glucan from the cell wall of Candida albicans (CaIG) was able to increase the production of of IL-6 and TNFa through Dectin-1-Syk-NF-kappa B and p38MAPK pathway. MiRNAs profiles combined with real-time PCR validation revealed that miR-146a, miR-30-5p, miR-210-3p expression level were increased in THP-1 cells treated with CaIG. The interaction between Dectin-1 and CaIG resulted in an long lasting increase of miR-146a expression dependent on Dectin-1-Syk-NF-kappa B, p38MAPK, contrasting with a rapid and transient increase of IL-6 and TNFa. Overexpression of miR-146a significantly suppressed the production of IL-6 and TNFa. MiR-146a mimics inhibited CaIG-induced activity of p-I kappa Ba and translocation of NF-kappa B p65. Luciferase reporter assays showed miR-146a inhibited NF-kappa B promoter-binding activity. Together, our data suggest miR-146a may play the potent negative feedback regulator in inflammatory response following Dectin-1 stimulation.