Animal models of Chlamydia pneumoniae and atherosclerosis: dissemination to and persistence in atheromatous lesions

Abstract

Chlamydia pneumoniae has been associated with atherosclerosis in humans. The goal of this dissertation is to evaluate animal models of both C. pneumoniae and atherosclerosis to investigate the pathogenesis of C. pneumoniae in atherosclerosis. New Zealand White (NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits and apolipoprotein, (apo)E-deficient transgenic and C57BL/6J mice were evaluated for susceptibility to C. pneumoniae infection.Following inoculation, NZW rabbits developed moderate self-resolving interstitial pneumonia. Chlamydial DNA was detected intermittently in the nasopharynx and lung through 42 days post-inoculation. In WHHL rabbits, C. pneumoniae was detected by PCR and/or immunocytochemistry in the nasopharynx and lung, but not within aortic atheromas, suggesting that rabbits, although susceptible to infection, were not appropriate for future studies.Following inoculation of apoE-deficient mice, C. pneumoniae was detected in lung, aorta and spleen for 20 weeks post-inoculation by PCR and within atherosclerotic lesions at 12 and 16 weeks post-inoculation by immunocytochemistry, indicating the suitability of this mouse model to study the role of C. pneumoniae in the progression of atherosclerosis. In C57BL/6J mice in the absence of a high fat diet, C. pneumoniae was detected in the aorta for 5 weeks after inoculation, suggesting this mouse model should be useful for studying the role of C. pneumoniae in the induction of atherosclerosis.To determine whether macrophages are a vehicle of dissemination, macrophages from C57BL/6J mice infected with C. pneumoniae were analyzed for their ability to support growth and transfer infection. C. pneumoniae was detected in alveolar and peritoneal macrophages and peripheral blood mononuclear cells of intranasally and/or intraperitoneally inoculated mice. When macrophages were transferred from infected to uninfected mice, C. pneumoniae DNA was detected in lung, spleen, abdominal lymph nodes and/or thymus.These results demonstrate the ability of C. pneumoniae to disseminate via macrophages in vivo. Persistence of C. pneumoniae within atheromas of apoE-deficient mice suggests tropism of the organism to the lesion indicating this animal model should be of benefit in examining whether infection alters the progression of atherosclerosis. The presence of C. pneumoniae in the aorta of C567BL/6J mice indicates this mouse model will be useful to investigate whether infection can induce atherosclerosis.