Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3

Clin Immunol. 2014 Apr;151(2):84-99. doi: 10.1016/j.clim.2014.01.010. Epub 2014 Feb 9.

Abstract

In this study, we explored the local cytokine/chemokine profiles in patients with active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of bronchoalveolar lavage and pleural fluid samples. Despite increased pro-inflammation compared to the uninfected controls; there was no up-regulation of IFN-γ or the T cell chemoattractant CCL5 in the lung of patients with pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4, CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN-γ, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2 immune response signature found in patients with progressive pulmonary TB could result from inappropriate cytokine/chemokine responses and excessive SOCS3 expression that may represent potential targets for clinical TB management.

Keywords: Cytokines; HIV; Human; Immune response; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cells, Cultured
  • Cytokines / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Regulation / immunology*
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / microbiology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Th2 Cells / immunology*
  • Tuberculosis, Pulmonary / immunology*
  • Young Adult

Substances

  • Cytokines
  • RNA, Messenger
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins