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

• Published in: The Journal of infectious diseases 2011-10, Vol.204 (7), p.1054-1064
• Main Authors: Basile, Juan I., Geffner, Laura J., Romero, María M., Balboa, Luciana, Sabio, Carmen, García, Carmen, Ritacco, Viviana, García, Ana, Cuffré, Mónica, Abbate, Eduardo, López, Beatriz, Barrera, Lucía, Ambroggi, Marta, Alemán, Mercedes, Sasiain, María, de la Barrera, Silvia S.
• Format: Article
• Language: English
• Subjects: Adult; Antigen presenting cells; Antigens; Antigens, Bacterial - immunology; BACTERIA; Bacteriology; Biological and medical sciences; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Cytokines; Female; Fundamental and applied biological sciences. Psychology; Humans; Infections; Infectious diseases; Interferon-gamma - metabolism; Interleukin-17 - metabolism; Interleukins; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Receptors; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Receptors, Interleukin - metabolism; Sputum; T lymphocytes; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Tuberculosis; Tuberculosis, Multidrug-Resistant - immunology; Young Adult
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir460

Background. The proinflammatoiy 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 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.