Apoptosis of Mycobacterium avium-infected macrophages is mediated by both tumour necrosis factor (TNF) and Fas, and involves the activation of caspases
Le. Bermudez et al., Apoptosis of Mycobacterium avium-infected macrophages is mediated by both tumour necrosis factor (TNF) and Fas, and involves the activation of caspases, CLIN EXP IM, 116(1), 1999, pp. 94-99
Mycobacterium avium causes disseminated infection in AIDS patients and seve
ral forms of infection in immunocompetent hosts. Recent studies have shown
that M. avium infection of macrophages in vitro leads to apoptosis of signi
ficant numbers of infected cells. Several strains of M. avium used to infec
t 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 i
ntracellularly (rep(-)) resulted in a 15% rate of apoptosis, while M. smegm
atis-infected monolayers showed the same percentage of apoptotic cells as t
he uninfected macrophage control. The presence of anti-TNF-alpha antibody r
educed apoptosis to 17% and the presence of anti-Fas antibody reduced apopt
osis to 10%. When both antibodies were used together, the apoptosis level w
as 5% above the control. Treatment with TGF-beta also reduced the number of
apoptotic cells in infected monolayers. If intracellular growth was inhibi
ted, apoptosis of macrophages decreased significantly. It was also shown th
at apoptosis was associated with IL-1 beta-converting enzyme (ICE) activati
on and was significantly reduced by a caspase inhibitor. Gaining understand
ing of the mechanisms of M. avium-associated apoptosis of macrophages will
provide important insight into M. avium pathogenesis.