Differential Induction of Apoptosis and Necrosis in Monocytes from Patients with Tuberculosis and Healthy Control Subjects

• Published in: The Journal of infectious diseases Vol. 189; no. 11; pp. 2120 - 2128
• Main Authors: Gil, Diana P., León, Laura G., Correa, Lucía I., Maya, José R., París, Sara C., García, Luis F., Rojas, Mauricio
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University Chicago Press 01.06.2004; University of Chicago Press; Oxford University Press
• Subjects: Adult; Aged; Apoptosis; Apoptosis - physiology; Bacteria; Bacterial diseases; Biological and medical sciences; Carbocyanines - chemistry; Cell death; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fluorescent Dyes - chemistry; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Humans; In Situ Nick-End Labeling; Infections; Infectious diseases; Interleukin-10 - biosynthesis; L-Lactate Dehydrogenase - metabolism; Macrophages; Male; Medical sciences; Microbiology; Middle Aged; Monocytes; Monocytes - metabolism; Monocytes - microbiology; Monocytes - pathology; Mycobacterium tuberculosis; Necrosis; Ploidies; Statistics, Nonparametric; T lymphocytes; Tuberculin; Tuberculin - pharmacology; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - pathology; Tumor Necrosis Factor-alpha - biosynthesis; Human; Infection; Tuberculosis; Microbiology; Monocyte; Cell death; Bacteriosis; Mycobacterial infection; Apoptosis; Necrosis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/386369

Background.Mycobacterium tuberculosis and puri?ed 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)-a-positive and interleukin (IL)-10-positive cells were determined cytofluorometrically. Levels of lactate dehydrogenase, TNF-α, and IL-10 were measured in culture supernatants. The role of TNF-α 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-α, whereas cells from patients with TB produced mainly IL-10. Blockade experiments suggest that TNF-α 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.