MicroRNA-146a promotes mycobacterial survival in macrophages through suppressing nitric oxide production

Miao Li, Jinli Wang, Yimin Fang, Sitang Gong, Meiyu Li, Minhao Wu, Xiaomin Lai, Gucheng Zeng, Yi Wang, Kun Yang, Xi Huang

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Macrophages play a crucial role in host innate anti-mycobacterial defense, which is tightly regulated by multiple factors, including microRNAs. Our previous study showed that a panel of microRNAs was markedly up-regulated in macrophages upon mycobacterial infection. Here, we investigated the biological function of miR-146a during mycobacterial infection. miR-146a expression was induced both in vitro and in vivo after Mycobacterium bovis BCG infection. The inducible miR-146a could suppress the inducible nitric oxide (NO) synthase (iNOS) expression and NO generation, thus promoting mycobacterial survival in macrophages. Inhibition of endogenous miR-146a increased NO production and mycobacterial clearance. Moreover, miR-146a attenuated the activation of nuclear factor ΰ B and mitogen-activated protein kinases signaling pathways during BCG infection, which in turn repressed iNOS expression. Mechanistically, miR-146a directly targeted tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) at post-transcriptional level. Silencing TRAF6 decreased iNOS expression and NO production in BCG-infected macrophages, while overexpression of TRAF6 reversed miR-146a-mediated inhibition of NO production and clearance of mycobacteria. Therefore, we demonstrated a novel role of miR-146a in the modulation of host defense against mycobacterial infection by repressing NO production via targeting TRAF6, which may provide a promising therapeutic target for tuberculosis.

Original languageEnglish (US)
Article number23351
JournalScientific reports
StatePublished - Mar 30 2016
Externally publishedYes

ASJC Scopus subject areas

  • General


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