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

MicroRNAs contribute to post-transcriptional controls that fine-tune protein expression. Cao and colleagues identify the microRNA miR-29 as a regulator of the expression of interferon-γ protein and show that intracellular infection with pathogens dampens miR-29 expression. 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 (T H 1) responses and greater resistance to infection with BCG or Mycobacterium tuberculosis . Therefore, miR-29 suppresses immune responses to intracellular pathogens by targeting IFN-γ.