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

F Ma, S Xu, X Liu, Q Zhang, X Xu, M Liu, M Hua… - Nature …, 2011 - nature.com
F Ma, S Xu, X Liu, Q Zhang, X Xu, M Liu, M Hua, N Li, H Yao, X Cao
Nature immunology, 2011nature.com
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 …
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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