Differential Early Secreted Antigen Target (ESAT) 6 kDa-induced IFN-γ and SOCS1 expression distinguishes latent and active tuberculosis

J Infect Dev Ctries. 2014 Jan 15;8(1):59-66. doi: 10.3855/jidc.3412.

Abstract

Introduction: Expression of Suppressor of cytokine signaling (SOCS)-1 molecules is increased in patients with tuberculosis (TB). Early Secreted Antigen Target (ESAT)-6 kDa - induced IFN-γ responses indicate Mycobacterium tuberculosis infection. The effect of ESAT6- stimulation on SOCS1 in the host is not known.

Methodology: Healthy asymptomatic controls had a negative (n = 16) or a positive ( n = 13) tuberculin skin test (TST). ESAT6-induced IFN-γ responses classified these controls as positive (EC ESAT6 IFN-γ (+), n = 5) or negative (EC ESAT6 IFN-γ (-), n = 24) responders. Patients had pulmonary (n = 21) or extra-pulmonary (n = 30) tuberculosis. Peripheral blood cells were stimulated with ESAT6 and mRNA expression of IFN-γ and SOCS1 was determined.

Results: ESAT6-induced IFN-γ expression was raised in EC ESAT6 IFN-γ (+) as compared with EC ESAT6 IFN-γ (-), p = 0.019. ESAT6-induced SOCS1 mRNA expression was increased in both pulmonary TB and extra-pulmonary TB patients as compared with both EC groups. ESAT6-induced IFN-γ/SOCS1 mRNA expression ratio was decreased in TB patients as compared with both EC groups.

Conclusion: M. tuberculosis infection induces increased ESAT6-induced IFN-γ responses in both latent and active TB. Our data shows down-regulation of IFN-γ / SOCS1 expression to be induced only in active TB cases, distinguishing them from healthy individuals likely to have latent TB. A decreasing IFN-γ /SOCS1 ratio may leads to reduced Th1 immunity which contributes to inability of the host to control clinical disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / immunology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / biosynthesis*
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology*
  • Young Adult

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interferon-gamma