CONICET | Buscador de Institutos y Recursos Humanos

Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-γ alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M. tuberculosis infection but the role of IL-17-producing cells in human tuberculosis remains to be understood. Therefore, we investigated the induction and regulation of IFN-γ and IL-17 during the active disease. Tuberculosis patients were classified as High and Low Responder individuals accordingly to their T cell responses against the antigen and cytokine expression upon M. tuberculosis stimulation was investigated in peripheral blood and pleural fluid. Afterwards, the potential correlation among the proportions of cytokine-producing cells and clinical parameters was analyzed. In tuberculosis patients, M. tuberculosis induced both IFN-γ and IL-17, but in comparison to BCG-vaccinated healthy controls, IFN-γ resulted significantly reduced and IL-17 was markedly augmented. Moreover, the main source of IL-17 was represented by CD4+IFN-γ+IL-17+ lymphocytes, a Th1/Th17 subset regulated by IFN-γ. Interestingly, the ratio of antigen-expanded CD4+IFN-γ+IL-17+ lymphocytes, in both peripheral blood and pleural fluid from tuberculosis patients, was directly correlated with clinical parameters associated with disease severity. Indeed, the highest proportion of CD4+IFN-γ+IL-17+ cells was detected in Low Responder tuberculosis patients, individuals displaying severe pulmonary lesions and longest length of disease evolution. Taken together, the present findings suggest that analysis of the expansion of CD4+IFN-γ+IL-17+ T lymphocytes in peripheral blood of tuberculosis patients might be employed as an indicator of the clinical outcome in active tuberculosis.