APOPTOSIS OF HUMAN MONOCYTES MACROPHAGES IN MYCOBACTERIUM-TUBERCULOSIS INFECTION/

Tuberculosis (TB) is still a major health problem, both as a single di sease entity and as a cofactor in AIDS. The interaction between macrop hage and Mycobacterium tuberculosis (MTB) is a critical step in the es tablishment of an early chronic infection, This study analyses the cap acity of MTB to induce apoptosis in cells obtained by broncho-alveolar lavage (BAL) from patients with reactive pulmonary tuberculosis and f rom AIDS patients with disseminated pulmonary tuberculosis, Apoptosis was increased three-fold in BAL cells obtained from patients with pulm onary tuberculosis and even more markedly in alveolar macrophages of M TB-infected AIDS patients, compared with controls, Apoptosis was analy sed and characterized by propidium iodide (PI) incorporation, terminal deoxy transferase (TDT)-mediated dUTP-biotin nick end labelling (TUNE L), and tissue transglutaminase (tTG) expression, The MTB-macrophage i nteraction was also investigated in vitro by infecting monocyte-derive d macrophages (MDM) with MTB (virulent strain H37Rv). The induction of apoptosis by MTB required viable bacteria, was dose-dependent, and wa s restricted to H37Rv. Infection with either Mycobacterium avium compl ex (MAC) or HIV-1 and treatment with heat-killed MTB failed to induce apoptosis.