Chlamydia pneumoniae Inhibits Apoptosis in Human Epithelial and Monocyte Cell Lines^*

Abstract

Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease. However, its immunopathogenic mechanisms are poorly understood. When aiming to study the impact of C. pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937‐line) were resistant to staurosporine and tumour necrosis factor (TNF)‐α‐induced physiological apoptosis 48, 72 or 120 h post‐infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy. The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation. We also found that during a persistent C. pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow‐up post‐infection and was restricted to the cells carrying chlamydial inclusions. Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C. pneumoniae infection can mediate the development of chronic diseases.

Mycoplasma fermentans inhibits tumor necrosis factor α-induced apoptosis in the human myelomonocytic U937 cell line

“…Therefore, we concluded that the effect of M. fermentans is upstream of the mitochondria. This result is similar to a recent observation regarding the effect of Chlamydia pneumoniae infection, 23,24 which was reported to render epithelial and monocyte cell lines resistant to TNFainduced apoptosis, via blockage of mitochondrial cytochrome c release.…”

“…Only a few papers have been published regarding inhibition of TNFa-induced apoptosis by Chlamydia pneumonia 23,24 and Hepatitis C Virus. 25 These support the hypothesis 26 that parasite bacteria might use a mechanism to prevent host cell apoptosis, in order to promote their survival and replication.…”

Chlamydia pneumoniaeActivates Epithelial Cell Proliferation via NF-κB and the Glucocorticoid Receptor

“…C. pneumoniae-dependent proliferation of the host cell, as well as cell damage, may alter the structure and function of the lung. Several studies indicate that C. pneumoniae inhibits apoptosis of monocytes and epithelial cells (1,3,27). Our data support these findings and furthermore suggest that C. pneumoniae infection leads to increased proliferation in epithelial cells.…”

Inhibition of caspase activation and a requirement for NF-κB function in theToxoplasma gondii-mediated blockade of host apoptosis

“…Several obligate intracellular bacteria [e.g. Chlamydia (Airenne et al, 2002;Fan et al, 1998;Geng et al, 2000;Perfettini et al, 2002), Rickettsiae (Clifton et al, 1998)] and protozoa [T. gondii (this study) (Goebel et al, 1998;Goebel et al, 1999;Goebel et al, 2001;Nash et al, 1998), Theileria spp. Heussler et al, 1999;Heussler et al, 2001)] actively suppress host apoptosis.…”