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Infection and Immunity, July 2005, p. 4315-4322, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4315-4322.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Chlamydia pneumoniae Augments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Kambiz Yaraei,¹ Lee Ann Campbell,¹ Xiaodong Zhu,² W. Conrad Liles,² Cho-chou Kuo,¹ and Michael E. Rosenfeld^1*

Departments of Pathobiology,¹ Medicine, University of Washington, Seattle, Washington²

Received 9 December 2004/ Returned for modification 3 February 2005/ Accepted 28 February 2005

Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 µg/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2.

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* Corresponding author. Mailing address: Department of Pathobiology, Box 353410, University of Washington, Seattle, WA 98195. Phone: (206) 543-1738. Fax: (206) 616-1245. E-mail: ssmjm{at}u.washington.edu.

Editor: J. N. Weiser

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Infection and Immunity, July 2005, p. 4315-4322, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4315-4322.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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