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We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis ( M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD+ HD)] by the M strain and the laboratory strain H37Rv. Our results show that IL-1β and IL-6 are crucial for the H37Rv and M-induced expansion of IL-17+interferon (IFN)-γ- and IL-17+IFN-γ+ in CD4+ T cells from MDR-TB and PPD+ HD. IL-23 plays an ambiguous role in T helper type 1 (Th1) and Th17 profiles: alone, IL-23 is responsible for M. tuberculosis-induced IL-17 and IFN-γ expression in CD4+ T cells from PPD+ HD whereas, together with transforming growth factor (TGF-β), it promotes IL-17+IFN-γ- expansion in MDR-TB. In fact, spontaneous and M. tuberculosis-induced TGF-β secretion is increased in cells from MDR-TB, the M strain being the highest inducer. Interestingly, Toll-like receptor (TLR)-2 signalling mediates the expansion of IL-17+IFN-γ- cells and the enhancement of latency-associated protein (LAP) expression in CD14+ and CD4+ T cells from MDR-TB, which suggests that the M strain promotes IL-17+IFN-γ- T cells through a strong TLR-2-dependent TGF-β production by antigen-presenting cells and CD4+ T cells. Finally, CD4+ T cells from MDR-TB patients infected with MDR Haarlem strains show higher IL-17+IFN-γ- and lower IL-17+IFN-γ+ levels than LAM-infected patients. The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response. [ABSTRACT FROM AUTHOR]

Tuberculous pleural effusion is characterized by a T helper type 1 ( Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells ( Treg) in the modulation of Th1 responses in patients with tuberculous ( TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg ( CD4+ CD25highforkhead box protein 3+), interferon ( IFN)-γ and interleukin ( IL)-10 expression and CD107 degranulation in peripheral blood ( PB) and pleural fluid ( PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4+ CD25+, CD4+ CD25high FoxP3+ and CD8+ CD25+ cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4+ CD25low/neg IL-10+ in PB and CD4+ CD25low/neg IFN-γ+ in PF; meanwhile, CD25high mainly expressed IL-10 in both compartments. A high proportion of CD4+ CD107+ and CD8+ CD107+ cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4+ and CD8+ degranulation responses and decreased CD4+ IL-10+ cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4+ and CD8+ cells to degranulate in response to M. tuberculosis. [ABSTRACT FROM AUTHOR]

We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD + HD)] by the M strain and the laboratory strain H37Rv. Our results show that IL-1β and IL-6 are crucial for the H37Rv and M-induced expansion of IL-17 + interferon (IFN)-γ - and IL-17 + IFN-γ + in CD4 + T cells from MDR-TB and PPD + HD. IL-23 plays an ambiguous role in T helper type 1 (Th1) and Th17 profiles: alone, IL-23 is responsible for M. tuberculosis-induced IL-17 and IFN-γ expression in CD4 + T cells from PPD + HD whereas, together with transforming growth factor (TGF-β), it promotes IL-17 + IFN-γ - expansion in MDR-TB. In fact, spontaneous and M. tuberculosis-induced TGF-β secretion is increased in cells from MDR-TB, the M strain being the highest inducer. Interestingly, Toll-like receptor (TLR)-2 signalling mediates the expansion of IL-17 + IFN-γ - cells and the enhancement of latency-associated protein (LAP) expression in CD14 + and CD4 + T cells from MDR-TB, which suggests that the M strain promotes IL-17 + IFN-γ - T cells through a strong TLR-2-dependent TGF-β production by antigen-presenting cells and CD4 + T cells. Finally, CD4 + T cells from MDR-TB patients infected with MDR Haarlem strains show higher IL-17 + IFN-γ - and lower IL-17 + IFN-γ + levels than LAM-infected patients. The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response., (© 2016 British Society for Immunology.)

Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (Treg ) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg (CD4(+) CD25(high) forkhead box protein 3(+) ), interferon (IFN)-γ and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4(+) CD25(+) , CD4(+) CD25(high) FoxP3(+) and CD8(+) CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+) CD25(low/neg) IL-10(+) in PB and CD4(+) CD25(low/neg) IFN-γ(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+) CD107(+) and CD8(+) CD107(+) cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4(+) and CD8(+) degranulation responses and decreased CD4(+) IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis., (© 2013 British Society for Immunology.)