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The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ

Nature Immunology volume 12, pages 861869 (2011) | Download Citation

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Abstract

Interferon-γ (IFN-γ) has a critical role in immune responses to intracellular bacterial infection. MicroRNAs (miRNAs) are important in the regulation of innate and adaptive immunity. However, whether miRNAs can directly target IFN-γ and regulate IFN-γ production post-transcriptionally remains unknown. Here we show that infection of mice with Listeria monocytogenes or Mycobacterium bovis bacillus Calmette-Guérin (BCG) downregulated miR-29 expression in IFN-γ-producing natural killer cells, CD4+ T cells and CD8+ T cells. Moreover, miR-29 suppressed IFN-γ production by directly targeting IFN-γ mRNA. We developed mice with transgenic expression of a 'sponge' target to compete with endogenous miR-29 targets (GS29 mice). We found higher serum concentrations of IFN-γ and lower L. monocytogenes burdens in L. monocytogenes–infected GS29 mice than in their littermates. GS29 mice had enhanced T helper type 1 (TH1) responses and greater resistance to infection with BCG or Mycobacterium tuberculosis. Therefore, miR-29 suppresses immune responses to intracellular pathogens by targeting IFN-γ.

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Change history

  • 04 April 2014

    In the version of this supplementary file originally posted online, the curves for the isotype-matched control antibodies in the plots for CD44 and CD62L in Supplementary Figure 7 were incorrect. The error has been corrected in this file as of 4 April 2014.

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Acknowledgements

We thank T. Chen, J. Hou and C. Han for discussions; Y. Li and M. Jin for technical support; C. Ni for pathological analysis; and H. Shen (University of Pennsylvania School of medicine) for L. monocytogenes. Supported by the National Key Basic Research Program of China (2007CB512403 and 2009CB521902), the National Natural Science Foundation of China (30721091, 30731160623), the Shanghai Committee of Science and Technology (10dz1910300) and the National High Biotechnology Development Program of China (2009ZX09503-003, 2009ZX09503-023).

Author information

Author notes

    • Feng Ma
    •  & Sheng Xu

    These authors contributed equally to this work.

Affiliations

  1. National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.

    • Feng Ma
    • , Sheng Xu
    • , Xingguang Liu
    • , Qian Zhang
    • , Xiongfei Xu
    • , Nan Li
    •  & Xuetao Cao
  2. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.

    • Feng Ma
    • , Hangping Yao
    •  & Xuetao Cao
  3. National Key Laboratory of Molecular Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

    • Mofang Liu
    •  & Minmin Hua
  4. National Key Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences, Beijing, China.

    • Xuetao Cao

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Contributions

X.C. and F.M. designed the experiments; F.M., S.X., X.L., Q.Z., X.X., M.L., M.H., N.L. and H.Y. did the experiments; and X.C., F.M. and S.X. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xuetao Cao.

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https://doi.org/10.1038/ni.2073