BACKGROUND: Mycobacterium tuberculosis and purified protein derivative (PPD) induce apoptosis in murine macrophages and apoptosis and necrosis in human monocytes and alveolar epithelial cells. Macrophages from bronchoalveolar lavages and granulomas from patients with tuberculosis (TB) present both types of cell death; however, the significance of the type of cell death in TB remains uncertain. METHODS: Monocytes from PPD-positive control subjects and from patients with TB were exposed to PPD or M. tuberculosis. Apoptosis, necrosis, and the percentage of tumor necrosis factor (TNF)-alpha -positive and interleukin (IL)-10-positive cells were determined cytofluorometrically. Levels of lactate dehydrogenase, TNF-alpha, and IL-10 were measured in culture supernatants. The role of TNF-alpha and IL-10 was tested by blockade experiments. RESULTS: PPD and M. tuberculosis induced apoptosis in monocytes from PPD-positive control subjects, whereas cells from patients with TB presented apoptosis and necrosis. Cells from PPD-positive control subjects produced mainly TNF-alpha, whereas cells from patients with TB produced mainly IL-10. Blockade experiments suggest that TNF-alpha and IL-10 regulate the type of cell death occurring in response to M. tuberculosis. CONCLUSIONS: Results suggest that apoptosis of monocytes exposed to mycobacteria may partly explain the protective immune response found in PPD-positive control subjects, whereas necrosis may be determinant of the bacterial dissemination and tissue damage that occur in patients with active TB.
BACKGROUND:Mycobacterium tuberculosis and purified protein derivative (PPD) induce apoptosis in murine macrophages and apoptosis and necrosis in human monocytes and alveolar epithelial cells. Macrophages from bronchoalveolar lavages and granulomas from patients with tuberculosis (TB) present both types of cell death; however, the significance of the type of cell death in TB remains uncertain. METHODS: Monocytes from PPD-positive control subjects and from patients with TB were exposed to PPD or M. tuberculosis. Apoptosis, necrosis, and the percentage of tumor necrosis factor (TNF)-alpha -positive and interleukin (IL)-10-positive cells were determined cytofluorometrically. Levels of lactate dehydrogenase, TNF-alpha, and IL-10 were measured in culture supernatants. The role of TNF-alpha and IL-10 was tested by blockade experiments. RESULTS: PPD and M. tuberculosis induced apoptosis in monocytes from PPD-positive control subjects, whereas cells from patients with TB presented apoptosis and necrosis. Cells from PPD-positive control subjects produced mainly TNF-alpha, whereas cells from patients with TB produced mainly IL-10. Blockade experiments suggest that TNF-alpha and IL-10 regulate the type of cell death occurring in response to M. tuberculosis. CONCLUSIONS: Results suggest that apoptosis of monocytes exposed to mycobacteria may partly explain the protective immune response found in PPD-positive control subjects, whereas necrosis may be determinant of the bacterial dissemination and tissue damage that occur in patients with active TB.
Authors: A Fortes; K Pereira; P R Z Antas; C L M C Franken; M Dalcolmo; M M Ribeiro-Carvalho; K S Cunha; A Geluk; A Kritski; A Kolk; P Klatser; E N Sarno; T H M Ottenhoff; E P Sampaio Journal: Clin Exp Immunol Date: 2005-09 Impact factor: 4.330
Authors: Adriana Aporta; Ainhoa Arbues; Juan I Aguilo; Marta Monzon; Juan J Badiola; Alba de Martino; Nadia Ferrer; Dessislava Marinova; Alberto Anel; Carlos Martin; Julian Pardo Journal: PLoS One Date: 2012-09-19 Impact factor: 3.240
Authors: Hugo Esquivel-Solís; Antonio J Vallecillo; Alejandro Benítez-Guzmán; L Garry Adams; Yolanda López-Vidal; José A Gutiérrez-Pabello Journal: PLoS One Date: 2013-05-15 Impact factor: 3.240