SOCS1 Antagonist-Expressing Recombinant Bacillus Calmette-Guérin Enhances Antituberculosis Protection in a Mouse Model

J Immunol. 2019 Jul 1;203(1):188-197. doi: 10.4049/jimmunol.1800694. Epub 2019 May 17.


Suppressor of cytokine signaling 1 (SOCS1) plays a key role in the negative regulation of JAK/STAT signaling, which is involved in innate immunity and subsequent adaptive immunity. Bacillus Calmette-Guérin (BCG) induces upregulation of SOCS1 expression in host cells, which may lead to the suppression of immune responses by BCG via inhibition of the JAK/STAT signaling pathway. This might cause A reduction in the protective effect of a BCG vaccine. In the current study, we assessed the immune responses to and the protective efficacy of a recombinant BCG secreting a dominant negative mutant of the SOCS1 molecule (rBCG-SOCS1DN). C57BL/6 mice were immunized with rBCG-SOCS1DN or parental BCG Tokyo vaccine strain harboring an empty plasmid vector (rBCG-pSO). rBCG-SOCS1DN enhanced the activation of bone marrow-derived dendritic cells and the activation of T cells compared with those with rBCG-pSO. The amounts of IFN-γ, TNF-α, and IL-6 produced by splenocytes of rBCG-SOCS1DN-immunized mice were larger than those produced by splenocytes of rBCG-pSO-immunized mice. Moreover, the rBCG-SOCS1DN-immunized mice showed a substantial reduction in the number of CFU of Mycobacterium tuberculosis in the lungs and spleens compared with that in control BCG-immunized mice when the immunized mice were infected with a highly pathogenic M. tuberculosis strain by inhalation. These findings provide evidence for the possibility of rBCG-SOCS1DN being an effective M. tuberculosis vaccine with a novel concept of rBCG as a tool for immunomodulation in host cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / genetics
  • BCG Vaccine / immunology*
  • Colony Count, Microbial
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunization
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mutation / genetics*
  • Mycobacterium tuberculosis / physiology*
  • RAW 264.7 Cells
  • Signal Transduction
  • Suppressor of Cytokine Signaling 1 Protein / antagonists & inhibitors
  • Suppressor of Cytokine Signaling 1 Protein / genetics*
  • T-Lymphocytes / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Vaccines, Synthetic / genetics


  • BCG Vaccine
  • Cytokines
  • Suppressor of Cytokine Signaling 1 Protein
  • Vaccines, Synthetic