Apoptosis of Mycobacterium avium‐infected macrophages is mediated by both tumour necrosis factor (TNF) and Fas, and involves the activation of caspases

• Published in: Clinical and experimental immunology Vol. 116; no. 1; pp. 94 - 99
• Main Authors: BERMUDEZ, L. E., PARKER, A., PETROFSKY, M.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.04.1999; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: apoptosis; Apoptosis - drug effects; Bacterial diseases; Biological and medical sciences; Caspase 1 - metabolism; Caspase Inhibitors; caspases; Caspases - metabolism; Enzyme Activation; fas Receptor - metabolism; Human bacterial diseases; Humans; Infectious diseases; macrophages; Macrophages - immunology; Macrophages - microbiology; Medical sciences; Mycabacterium avium; Mycobacterium avium; Mycobacterium avium - immunology; Mycobacterium smegmatis - immunology; Original; Signal Transduction; Tuberculosis and atypical mycobacterial infections; Tumor Necrosis Factor-alpha - metabolism; Human; Fas antigen; Pathophysiology; Cytokine; Mycobacterium avium; Caspase; In vitro; Defense; Infection; Membrane receptor; Mycobacteriales; Mycobacteriaceae; Bacteriosis; Bacteria; Tumor necrosis factor β; Actinomycetes; Tumor necrosis factor α; Apoptosis; Macrophage; Biological receptor
• DOI: 10.1046/j.1365-2249.1999.00852.x
• ISSN: 0009-9104

Mycobacterium avium causes disseminated infection in AIDS patients and several forms of infection in immunocompetent hosts. Recent studies have shown that M. avium infection of macrophages in vitro leads to apoptosis of significant numbers of infected cells. Several strains of M. avium used to infect human macrophages for 5 days (multiplicity of infection of 10) triggered 28–46% higher levels of apoptosis than observed with uninfected macrophages at the same time points. Mycobacterium avium strains unable to replicate intracellularly (rep−) resulted in a 15% rate of apoptosis, while M. smegmatis‐infected monolayers showed the same percentage of apoptotic cells as the uninfected macrophage control. The presence of anti‐TNF‐α antibody reduced apoptosis to 17% and the presence of anti‐Fas antibody reduced apoptosis to 10%. When both antibodies were used together, the apoptosis level was 5% above the control. Treatment with TGF‐β also reduced the number of apoptotic cells in infected monolayers. If intracellular growth was inhibited, apoptosis of macrophages decreased significantly. It was also shown that apoptosis was associated with IL‐1β‐converting enzyme (ICE) activation and was significantly reduced by a caspase inhibitor. Gaining understanding of the mechanisms of M. avium‐associated apoptosis of macrophages will provide important insight into M. avium pathogenesis.