Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism

Nat Immunol. 2016 Jun;17(6):677-86. doi: 10.1038/ni.3434. Epub 2016 Apr 18.


Mycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy. These data define a mammalian miRNA circuit used by Mtb to coordinately inhibit autophagy and reprogram host lipid metabolism to enable intracellular survival and persistence in the host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Cells, Cultured
  • Host-Pathogen Interactions
  • Humans
  • Immune Evasion
  • Lipid Metabolism / genetics*
  • Lysosomes / microbiology
  • Lysosomes / physiology*
  • Macrophages / microbiology
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mycobacterium tuberculosis / physiology*
  • Signal Transduction
  • Transcription Factors / metabolism
  • Tuberculosis / genetics*


  • MicroRNAs
  • Mirn33 microRNA, mouse
  • Transcription Factors