MicroRNA-146a Represses Mycobacteria-Induced Inflammatory Response and Facilitates Bacterial Replication via Targeting IRAK-1 and TRAF-6

BACKGROUND: Apart from triggering host immune responses, macrophages also act as a major reservoir for mycobacteria. For better survival, mycobacteria have evolved various mechanisms to modulate the production of proinflammatory cytokines in macrophages, and manipulation of micro-RNA (miRNA) expression has been considered as an important one. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we found that miR-146a expression was significantly increased in a time- and dose-dependent manner in mycobacteria-infected macrophages. It could obviously reduce the induction of proinflammatory cytokines TNF-α, IL-1β, IL-6 and chemokine MCP-1 by targeting interleukin-1 receptor-associated kinase-1 (IRAK-1) and TNF receptor-associated factor-6 (TRAF-6), two key elements involved in the TLR/NF-κB signaling pathway cascades. Consistent with the anti-inflammation effect, a higher bacterial burden was seen in miR-146a mimics-treated macrophages. CONCLUSION/SIGNIFICANCE: Here, we demonstrated that mycobacteria-induced miR-146a could modulate inflammatory response by targeting IRAK1 and TRAF6 and facilitate mycobacteria replication in macrophages.