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Infection and Immunity, November 2001, p. 7121-7129, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.7121-7129.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Characterization of Antiapoptotic Activities of Chlamydia pneumoniae in Human Cells

Silke F. Fischer, Claudia Schwarz, Juliane Vier, and Georg Häcker*

Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany

Received 23 May 2001/Returned for modification 17 July 2001/Accepted 3 August 2001

Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in atherosclerosis. Here we show that infection with C. pneumoniae protects HeLa human epithelioid cells against apoptosis induced by external stimuli. In infected HeLa cells, apoptosis induced by staurosporine and CD95-death-receptor signaling was strongly reduced. Upon treatment with staurosporine, generation of effector caspase activity, processing of caspase-3 and caspase-9 and cytochrome c redistribution were all profoundly inhibited in cells infected with C. pneumoniae. Bacterial protein synthesis during early infection was required for this inhibition. Furthermore, cytochrome c-induced processing and activation of caspases were inhibited in cytosolic extracts from infected cells, suggesting that a C. pneumoniae-dependent antiapoptotic factor was generated in the cytosol upon infection. Infection with C. pneumoniae failed to induce significant NF-kappa B activation in HeLa cells, indicating that no NF-kappa B-dependent cellular factors were involved in the protection against apoptosis. These results show that C. pneumoniae is capable of interfering 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.

* Corresponding author. Mailing address: Georg Häcker, Institute for Medical Microbiology, Technische Universität München, Trogerstr. 9, D-81675 Munich, Germany. Phone: 49 89 4140 4121. Fax: 49 89 4140 4868. E-mail: hacker{at}lrz.tum.de.

Infection and Immunity, November 2001, p. 7121-7129, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.7121-7129.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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