The Tim3-galectin 9 pathway induces antibacterial activity in human macrophages infected with Mycobacterium tuberculosis

J Immunol. 2012 Dec 15;189(12):5896-902. doi: 10.4049/jimmunol.1200990. Epub 2012 Nov 23.


T cell Ig and mucin domain 3 (Tim3) is an inhibitory molecule involved in immune tolerance, autoimmune responses, and antiviral immune evasion. However, we recently demonstrated that Tim3 and Galectin-9 (Gal9) interaction induces a program of macrophage activation that results in killing of Mycobacterium tuberculosis in the mouse model of infection. In this study, we sought to determine whether the Tim3-Gal9 pathway plays a similar role in human pulmonary TB. We identified that pulmonary TB patients have reduced expression of Tim3 on CD14(+) monocytes in vivo. By blocking Tim3 and Gal9 interaction in vitro, we show that these molecules contribute to the control of intracellular bacterial replication in human macrophages. The antimicrobial effect was partially dependent on the production of IL-1β. Our results establish that Tim3-Gal9 interaction activates human M. tuberculosis -infected macrophages and leads to the control of bacterial growth through the production of the proinflammatory cytokine IL-1β. Data presented in this study suggest that one of the potential pathways activated by Tim3/Gal9 is the secretion of IL-1β, which plays a crucial role in antimicrobial immunity by modulating innate inflammatory networks.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Blocking / biosynthesis
  • Antibodies, Blocking / physiology*
  • Female
  • Galectins / antagonists & inhibitors
  • Galectins / immunology
  • Galectins / physiology*
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Male
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / immunology
  • Membrane Proteins / physiology*
  • Middle Aged
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / immunology*
  • Protein Interaction Mapping
  • Signal Transduction / immunology*


  • Antibodies, Blocking
  • Galectins
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • LGALS9 protein, human
  • Membrane Proteins