Chlamydia pneumoniae inhibits apoptosis in human epithelial and monocyte cell lines.
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)-alpha-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.
Airenne
S
S
National Public Health Institute, Oulu, Finland. sari.airenne@ktl.fi
Surcel
H-M
HM
Tuukkanen
J
J
Leinonen
M
M
Saikku
P
P
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000472:pathogenicity*; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology; D009000:Monocytes / Q000382:microbiology / Q000502:physiology*; D010406:Penicillins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003574:Cytochrome c Group; D010406:Penicillins; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases