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Pseudomonas aeruginosa infection augments inflammation through miR-301b repression of c-Myb-mediated immune activation and infiltration

Nature Microbiology volume 1, Article number: 16132 (2016) | Download Citation

Abstract

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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Acknowledgements

This work was supported by the National Institutes of Health (AI109317-01A1 and AI101973-01) to M.W., and by grants from the National 973 Basic Research Program of China (2013CB911300), the Chinese NSFC (81225015 and 81430071) and Sichuan Science–Technology Innovative Research Team for Young Scientist (2013TD0001) to C.H. The authors thank S. Abrahamson of the UND imaging core for help with confocal imaging.

Author information

Author notes

    • Xuefeng Li
    • , Sisi He
    • , Rongpeng Li
    •  & Xikun Zhou

    These authors contributed equally to this work.

Affiliations

  1. Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota 58203-9037, USA

    • Xuefeng Li
    • , Sisi He
    • , Rongpeng Li
    • , Xikun Zhou
    • , Shuang Zhang
    • , Min Yu
    • , Yan Ye
    •  & Min Wu
  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China

    • Xuefeng Li
    • , Sisi He
    • , Xikun Zhou
    • , Shuang Zhang
    • , Yongsheng Wang
    •  & Canhua Huang
  3. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu 610041, China

    • Min Yu

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Contributions

X.L., S.H., C.H. and M.W conceived and designed the experiments. X.L., S.H., R.L. and X.Z. performed the experiments. X.L., S.H., R.L., X.Z., S.Z., M.Y., Y.Y. and Y.W. analysed the data. C.H. and M.W. contributed reagents, materials and analysis tools. X.L., S.H., C.H. and M.W. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Canhua Huang or Min Wu.

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DOI

https://doi.org/10.1038/nmicrobiol.2016.132

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