Expression of inhibitory regulators of innate immunity in patients with active tuberculosis

BMC Infect Dis. 2015 Feb 26;15:98. doi: 10.1186/s12879-015-0833-z.

Abstract

Background: Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Toll-like-receptors (TLRs) are important for the recognition of the causative agent Mycobacterium tuberculosis. Negative regulation of TLRs is necessary to control deleterious inflammatory damage, but could provide a means of immune evasion by M. tuberculosis as well.

Methods: To obtain insight in the extent of expression of inhibitory regulators of immunity in patients with active TB, peripheral-blood-mononuclear-cells (PBMCs) and plasma were obtained from 54 TB patients and 29 healthy blood donors from Chittagong, Bangladesh. Bilateral alveolar macrophages were obtained from an infected versus a contralateral normal lung segment of 9 patients. Statistical analyses were performed using Mann-Whitney U and Wilcoxon matched pairs testing. Correlations were calculated using the Spearman rho test.

Results: PBMCs harvested from TB patients demonstrated increased mRNA expression of IL-1-receptor-associated-kinase-M, suppressor-of-cytokine-signalling-3 and Toll-interacting-protein. Flow cytometry revealed enhanced expression of IL-1-receptor-like-1 (ST2) on lymphocytes. Plasma soluble ST2 was elevated in patients with TB and correlated with established TB biomarkers, most strongly with soluble interleukin-2 receptor subunit α and interleukin-8. Alveolar macrophage mRNA expression of negative TLR regulators did not differ between the infected and contralateral lung side.

Conclusion: These results show enhanced expression of distinct negative regulators of innate immunity in PBMCs of patients with TB and identify plasma soluble ST2 as a potential novel biomarker for TB disease activity.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bangladesh / epidemiology
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Innate / immunology*
  • Interleukin-8 / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Toll-Like Receptors / immunology
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / immunology*
  • Young Adult

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Toll-Like Receptors