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

BASILE JI; GEFFNER L; ROMERO MM; BALBOA L; SABIO Y GARCÍA C; RITACCO V; GARCÍA A; CUFFRÉ M; ABBATE E; LOPEZ B; BARRERA L; AMBROGGI M; ALEMÁN M; SASIAIN MC; DE LA BARRERA S

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Año: 2011 vol. 204 p. 1054 - 1064

0022-1899

Background: The pro-inflammatory cytokine 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 patients (TB) and in healthy human tuberculin reactors (PPD+HD). Methods: IL-17, IFN-and IL-23 receptor expression were evaluated in 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 drugsusceptible isolates belonging to the same families and laboratory strain H37Rv for 48hs in T cell subsets by flow cytometry. Results: We observed that: i) MDR strains M and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the Haarlem and Latin-American Mediterranean families, ii) MDR-TB patients show the highest IL-17 expression that is independent on the strain, iii) 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 to the low effectiveness of the second line drugs employed in the treatment.