IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
Restimulation-induced T-cell death through NTB-A/SAP signaling pathway is impaired in tuberculosis patients with depressed immune responses
Autor/es:
HERNÁNDEZ DEL PINO, RODRIGO E.; PENÃ, DELFINA; MUSELLA, ROSA M.; PASQUINELLI, VIRGINIA; PELLEGRINI, JOAQUÍN M.; ÁLVAREZ, GUADALUPE I.; PALMERO, DOMINGO J.; GARCIÁ, VERÓNICA E.; ROVETTA, ANA I.; ROLANDELLI, AGUSTÍN; MALBRAN, ALEJANDRO; PELLEGRINI, JOAQUÍN M.; HERNÁNDEZ DEL PINO, RODRIGO E.; ÁLVAREZ, GUADALUPE I.; PENÃ, DELFINA; MUSELLA, ROSA M.; PALMERO, DOMINGO J.; PASQUINELLI, VIRGINIA; GARCIÁ, VERÓNICA E.; ROVETTA, ANA I.; ROLANDELLI, AGUSTÍN; MALBRAN, ALEJANDRO
Revista:
IMMUNOLOGY AND CELL BIOLOGY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2017 vol. 95 p. 716 - 728
ISSN:
0818-9641
Resumen:
Production of IFN-γ3 contributes to host defense against Mycobacterium tuberculosis (Mtb) infection. We previously demonstrated that Signaling lymphocytic activation molecule-associated protein (SAP) expression on cells from tuberculosis (TB) patients was inversely correlated with IFN-γ3 production. Here we first investigated the role of NK, T- A nd B-cell antigen (NTB-A)/SAP pathway in the regulation of Th1 response against Mtb. Upon antigen stimulation, NTB-A phosphorylation rapidly increases and afterwards modulates IFN-γ3 and IL-17 secretion. To sustain a healthy immune system, controlled expansion and contraction of lymphocytes, both during and after an adaptive immune response, is essential. Besides, restimulation-induced cell death (RICD) results in an essential homeostatic mechanism for precluding excess T-cell accumulation and associated immunopathology during the course of certain infections. Accordingly, we found that the NTB-A/SAP pathway was required for RICD during active tuberculosis. In low responder (LR) TB patients, impaired RICD was associated with diminished FASL levels, IL-2 production and CD25high expression after cell-restimulation. Interestingly, we next observed that SAP mediated the recruitment of the Src-related kinase FYNT, only in T cells from LR TB patients that were resistant to RICD. Together, we showed that the NTB-A/SAP pathway regulates T-cell activation and RICD during human TB. Moreover, the NTB-A/SAP/FYNT axis promotes polarization to an unfavorable Th2-phenotype.