Primary Role of Suppressor of Cytokine Signaling 1 in Mycobacterium bovis BCG Infection

Infect Immun. 2018 Oct 25;86(11):e00376-18. doi: 10.1128/IAI.00376-18. Print 2018 Nov.


Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of JAK/STAT signaling and is induced by mycobacterial infection. To understand the major function of SOCS1 during infection, we established a novel system in which recombinant Mycobacterium bovis bacillus Calmette-Guérin expressed dominant-negative SOCS1 (rBCG-SOCS1DN) because it would not affect the function of SOCS1 in uninfected cells. When C57BL/6 mice and RAG1-/- mice were intratracheally inoculated with rBCG-SOCS1DN, the amount of rBCG-SOCS1DN in the lungs was significantly reduced compared to that in the lungs of mice inoculated with a vector control counterpart and wild-type BCG. However, these significant differences were not observed in NOS2-/- mice and RAG1-/- NOS2-/- double-knockout mice. These findings demonstrated that SOCS1 inhibits nitric oxide (NO) production to establish mycobacterial infection and that rBCG-SOCS1DN has the potential to be a powerful tool for studying the primary function of SOCS1 in mycobacterial infection.

Keywords: Mycobacterium bovis BCG; Mycobacterium tuberculosis; SOCS1; nitric oxide; recombinant BCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Host-Pathogen Interactions*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium bovis / growth & development*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / deficiency
  • Nitric Oxide Synthase Type II / metabolism
  • Signal Transduction*
  • Suppressor of Cytokine Signaling 1 Protein / genetics
  • Suppressor of Cytokine Signaling 1 Protein / metabolism*
  • Tuberculosis / microbiology*
  • Tuberculosis / pathology*


  • Homeodomain Proteins
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • RAG-1 protein
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse