Pseudomonas aeruginosa infection augments inflammation through miR-301b repression of c-Myb-mediated immune activation and infiltration
NATURE MICROBIOLOGY(2016)
摘要
MicroRNAs (miRNAs) play critical roles in various biological processes, including cell proliferation, development and host defence. However, the molecular mechanism for miRNAs in regulating bacterial-induced inflammation remains largely unclear. Here, we report that miR-301b augments pro-inflammatory response during pulmonary infection, and caffeine suppresses the effect of miR-301b and thereby augments respiratory immunity. LPS treatment or Pseudomonas aeruginosa infection induces miR-301b expression via a TLR4/MyD88/NF-κB pathway. Importantly, caffeine decreases miR-301b expression through negative regulation of the cAMP/PKA/NF-κB axis. Further, c-Myb is identified as a target of miR-301b, which positively modulates anti-inflammatory cytokines IL-4 and TGF-β1, but negatively regulates pro-inflammatory cytokines MIP-1α and IL-17A. Moreover, repression of miR-301b results in increased transcription of c-Myb and elevated levels of neutrophil infiltration, thereby alleviating infectious symptoms in mice. These findings reveal miR-301b as a new controller of inflammatory response by repressing c-Myb function to inhibit the anti-inflammatory response to bacterial infection, representing a novel mechanism for balancing inflammation.
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关键词
Antimicrobial responses,Bacterial host response,Bacterial pathogenesis,miRNAs,Pathogens,Life Sciences,general,Microbiology,Medical Microbiology,Parasitology,Infectious Diseases,Virology
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