title: 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.
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.
authors: Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors: Juan I
authors: JI
authors: Basile
authors: Laura J
authors: LJ
authors: Geffner
authors: María M
authors: MM
authors: Romero
authors: Luciana
authors: L
authors: Balboa
authors: Carmen
authors: C
authors: Sabio Y García
authors: Viviana
authors: V
authors: Ritacco
authors: Ana
authors: A
authors: García
authors: Mónica
authors: M
authors: Cuffré
authors: Eduardo
authors: E
authors: Abbate
authors: Beatriz
authors: B
authors: López
authors: Lucía
authors: L
authors: Barrera
authors: Marta
authors: M
authors: Ambroggi
authors: Mercedes
authors: M
authors: Alemán
authors: María C
authors: MC
authors: Sasiain
authors: Silvia S
authors: SS
authors: de la Barrera
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; C515500:IL23R protein, human; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D007371:Interferon-gamma