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

Nat Immunol. 2011 Jul 24;12(9):861-9. doi: 10.1038/ni.2073.

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 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity* / genetics
  • Adaptive Immunity* / immunology
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cattle
  • Colony Count, Microbial
  • Gene Silencing
  • Immunity, Innate* / genetics
  • Immunity, Innate* / immunology
  • Interferon-gamma* / antagonists & inhibitors
  • Interferon-gamma* / genetics
  • Interferon-gamma* / immunology
  • Interferon-gamma* / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lentivirus
  • Listeria monocytogenes / growth & development
  • Listeriosis / immunology
  • Listeriosis / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs* / antagonists & inhibitors
  • MicroRNAs* / immunology
  • MicroRNAs* / metabolism
  • Mycobacterium bovis / growth & development
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / metabolism
  • Th1-Th2 Balance
  • Transfection
  • Tuberculosis, Bovine / immunology
  • Tuberculosis, Bovine / microbiology

Substances

  • MicroRNAs
  • RNA, Messenger
  • Interferon-gamma