Differential induction of apoptosis and necrosis in monocytes from patients with tuberculosis and healthy control subjects.
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.
Gil
Diana P
DP
Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.
León
Laura G
LG
Correa
Lucía I
LI
Maya
José R
JR
París
Sara C
SC
García
Luis F
LF
Rojas
Mauricio
M
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D002232:Carbocyanines / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D009169:Mycobacterium tuberculosis; D009336:Necrosis; D011003:Ploidies; D018709:Statistics, Nonparametric; D014373:Tuberculin / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D002232:Carbocyanines; D005456:Fluorescent Dyes; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; D007770:L-Lactate Dehydrogenase