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.
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: Uma Shanmugasundaram; Allison N Bucsan; Shashank R Ganatra; Chris Ibegbu; Melanie Quezada; Robert V Blair; Xavier Alvarez; Vijayakumar Velu; Deepak Kaushal; Jyothi Rengarajan Journal: JCI Insight Date: 2020-07-23
Authors: Nancy Vázquez; Sofia Rekka; Maria Gliozzi; Carl G Feng; Shoba Amarnath; Jan M Orenstein; Sharon M Wahl Journal: J Infect Dis Date: 2012-08-28 Impact factor: 5.226
Authors: Keertan Dheda; Tawanda Gumbo; Neel R Gandhi; Megan Murray; Grant Theron; Zarir Udwadia; G B Migliori; Robin Warren Journal: Lancet Respir Med Date: 2014-03-24 Impact factor: 30.700
Authors: J I Basile; D Kviatcovsky; M M Romero; L Balboa; J Monteserin; V Ritacco; B Lopez; C Sabio y García; A García; M Vescovo; P G Montaner; D Palmero; M Del Carmen Sasiain; S de la Barrera Journal: Clin Exp Immunol Date: 2016-11-02 Impact factor: 4.330