Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection.
Tuberculosis (TB) is still a major health problem, both as a single disease entity and as a cofactor in AIDS. The interaction between macrophage and Mycobacterium tuberculosis (MTB) is a critical step in the establishment of an early chronic infection. This study analyses the capacity of MTB to induce apoptosis in cells obtained by broncho-alveolar lavage (BAL) from patients with reactive pulmonary tuberculosis and from AIDS patients with disseminated pulmonary tuberculosis. Apoptosis was increased three-fold in BAL cells obtained from patients with pulmonary tuberculosis and even more markedly in alveolar macrophages of MTB-infected AIDS patients, compared with controls. Apoptosis was analysed and characterized by propidium iodide (PI) incorporation, terminal deoxy transferase (TDT)-mediated dUTP-biotin nick end labelling (TUNEL), and tissue transglutaminase (tTG) expression. The MTB-macrophage interaction was also investigated in vitro by infecting monocyte-derived macrophages (MDM) with MTB (virulent strain H37Rv). The induction of apoptosis by MTB required viable bacteria, was dose-dependent, and was restricted to H37Rv. Infection with either Mycobacterium avium complex (MAC) or HIV-1 and treatment with heat-killed MTB failed to induce apoptosis.
Placido
R
R
Department of Biology University of Rome Tor Vergata, Italy.
Mancino
G
G
Amendola
A
A
Mariani
F
F
Vendetti
S
S
Piacentini
M
M
Sanduzzi
A
A
Bocchino
M L
ML
Zembala
M
M
Colizzi
V
V
D017088:AIDS-Related Opportunistic Infections / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018929:Cell Culture Techniques; D005260:Female; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D011503:Transglutaminases / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000473:pathology*
D011503:Transglutaminases