Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity

Tuberculosis (Edinb). 2015 May;95(3):267-74. doi: 10.1016/j.tube.2015.03.004. Epub 2015 Mar 21.

Abstract

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection.

Keywords: Mucosal-associated invariant T cells; Mycobacterium tuberculosis; Nontuberculous mycobacteria; Programmed death-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cell Line
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Mucosal*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interferon-gamma Release Tests
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / diagnosis
  • Mycobacterium Infections, Nontuberculous / immunology*
  • Mycobacterium Infections, Nontuberculous / metabolism
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Mycobacterium tuberculosis / immunology*
  • Predictive Value of Tests
  • Programmed Cell Death 1 Receptor / metabolism
  • Sputum / microbiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / microbiology
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / metabolism
  • Tuberculosis, Pulmonary / microbiology

Substances

  • IFNG protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interferon-gamma