Characterization of antiapoptotic activities of Chlamydia pneumoniae in human cells

Chlamydia pneumoniae is an obligate intracellular bacterium which frequentl y causes airway infection in humans and has been implicated in atherosclero sis. Here we show that infection with C. pneumoniae protects HeLa human epi thelioid cells against apoptosis induced by external stimuli. In infected H eLa cells, apoptosis induced by staurosporine and CD95-death-receptor signa ling was strongly reduced. Upon treatment with staurosporine, generation of effector caspase activity, processing of caspase-3 and caspase-9 and cytoc hrome c redistribution were all profoundly inhibited in cells infected with C. pneumoniae. Bacterial protein synthesis during early infection was requ ired for this inhibition. Furthermore, cytochrome c-induced processing and activation of caspases were inhibited in cytosolic extracts from infected c ells, suggesting that a C. pneumoniae-dependent antiapoptotic factor was ge nerated in the cytosol upon infection. Infection with C. pneumoniae failed to induce significant NF-kappaB activation in HeLa cells, indicating that n o NF-kappaB-dependent cellular factors were involved in the protection agai nst apoptosis. These results show that C. pneumoniae is capable of interfer ing with the host cell's apoptotic apparatus at probably at least two steps in signal transduction and might explain the propensity of these bacteria to cause chronic infections in humans.