National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
Nat Immunol. 2011 Jul 24;12(9):861-9. doi: 10.1038/ni.2073.
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.
干扰素-γ（IFN-γ）在针对细胞内细菌感染的免疫反应中起着关键作用。微小 RNA（miRNA）在先天和适应性免疫的调节中很重要。然而，miRNA 是否可以直接靶向 IFN-γ并在转录后调节 IFN-γ 的产生仍不清楚。在这里，我们发现李斯特菌或牛分枝杆菌卡介苗（BCG）感染小鼠后，IFN-γ 产生的自然杀伤细胞、CD4(+)T 细胞和 CD8(+)T 细胞中 miR-29 的表达下调。此外，miR-29 通过直接靶向 IFN-γ mRNA 抑制 IFN-γ 的产生。我们开发了一种转染表达“海绵”靶标的小鼠，以与内源性 miR-29 靶标竞争（GS29 小鼠）。我们发现，感染李斯特菌的 GS29 小鼠的血清 IFN-γ 浓度更高，李斯特菌负荷更低。GS29 小鼠具有增强的 T 辅助型 1（T(H)1）反应和对 BCG 或结核分枝杆菌感染的抵抗力更强。因此，miR-29 通过靶向 IFN-γ 抑制对细胞内病原体的免疫反应。
