Outbreaks of mycobacterium tuberculosis MDR strains induce high IL-17 T-cell response in patients with MDR tuberculosis that is closely associated with high antigen load

J Infect Dis. 2011 Oct 1;204(7):1054-64. doi: 10.1093/infdis/jir460.

Abstract

Background: The proinflammatory cytokine interleukin 17 (IL-17) plays an important role in immune responses but it is also associated with tissue-damaging inflammation. So, we evaluated the ability of Mycobacterium tuberculosis clinical isolates to induce IL-17 in tuberculosis (TB) patients and in healthy human tuberculin reactors (PPD(+)HD).

Methods: IL-17, interferon γ (IFN-γ), and interleukin 23 (IL-23) receptor expression were evaluated ex vivo and cultured peripheral blood mononuclear cells from TB and PPD(+)HD stimulated with irradiated clinical isolates from multidrug resistant (MDR) outbreaks M (Haarlem family) and Ra (Latin American-Mediterranean family), as well as drug-susceptible isolates belonging to the same families and laboratory strain H37Rv for 48 hours in T-cell subsets by flow cytometry.

Results: We observed that: (1) MDR strains M and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the Haarlem and Latin American-Mediterranean families, (2) MDR-TB patients show the highest IL-17 expression that is independent on the strain, (3) IL-17 expression is dependent on CD4(+) and CD8(+) T cells associates with persistently high antigen load.

Conclusions: IL-17--producing T cells could play an immunopathological role in MDR-TB promoting severe tissue damage, which may be associated with the low effectiveness of the second-line drugs employed in the treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, Interleukin / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Tuberculosis, Multidrug-Resistant / immunology*
  • Young Adult

Substances

  • Antigens, Bacterial
  • IL23R protein, human
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin
  • Interferon-gamma