Mycobacterium tuberculosis multi-drug-resistant strain M induces IL-17+ IFNγ- CD4+ T cell expansion through an IL-23 and TGF-β-dependent mechanism in patients with MDR-TB tuberculosis.

BASILE JI; BALBOA L; KVIATCOVSKY D; LOPEZ B; VESCOVO M; MONTESERIN J; SASIAIN MARÍA DEL CARMEM; SABIO Y GARCÍA C; KVIATCOVSKY D; GONZALEZ MONTANER P; MONTESERIN J; DE LA BARRERA SILVIA; SABIO Y GARCÍA C; ROMERO M; GONZALEZ MONTANER P; RITACCO V; DE LA BARRERA SILVIA; GARCÍA A; PALMERO DOMINGO; ROMERO M; RITACCO V; GARCÍA A; PALMERO DOMINGO; BASILE JI; BALBOA L; LOPEZ B; VESCOVO M; SASIAIN MARÍA DEL CARMEM

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2017 vol. 187 p. 160 - 173

0009-9104

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.