Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-gamma (IFN-gamma)-dependent manner

J Biol Chem. 2011 Jul 29;286(30):26873-87. doi: 10.1074/jbc.M111.238287. Epub 2011 May 27.


Protection against infection with Mycobacterium tuberculosis demands IFN-γ. SOCS1 has been shown to inhibit responses to IFN-γ and might thereby play a central role in the outcome of infection. We found that M. tuberculosis is a highly efficient stimulator of SOCS1 expression in murine and human macrophages and in tissues from infected mice. Surprisingly, SOCS1 reduced responses to IL-12, resulting in an impaired IFN-γ secretion by macrophages that in turn accounted for a deteriorated intracellular mycobacterial control. Despite SOCS1 expression, mycobacteria-infected macrophages responded to exogenously added IFN-γ. SOCS1 attenuated the expression of the majority of genes modulated by M. tuberculosis infection of macrophages. Using a conditional knockdown strategy in mice, we found that SOCS1 expression by macrophages hampered M. tuberculosis clearance early after infection in vivo in an IFN-γ-dependent manner. On the other hand, at later time points, SOCS1 expression by non-macrophage cells protected the host from infection-induced detrimental inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Gene Silencing
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / metabolism*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Tuberculosis / genetics
  • Tuberculosis / immunology
  • Tuberculosis / metabolism*


  • SOCS1 protein, human
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interleukin-12
  • Interferon-gamma