Experimental Chlamydia pneumoniae infection model: effects of repeated inoculations and treatment
|Organizations:||University of Oulu, Faculty of Medicine, Department of Medical Microbiology
National Public Health Institute, Department of Viral Diseases and Immunology
|Online Access:||PDF Full Text (PDF, 3.2 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:951427976X
|Publish Date:|| 2006-01-16
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of Kastelli Research Center (Aapistie 1), on January 21st, 2006, at 10 a.m.
Professor Ignatius W. Fong
Docent Kimmo Mattila
Chlamydia pneumoniae is a common human pathogen worldwide, which causes both upper and lower respiratory tract infections. In addition, C. pneumoniae infections have been associated with atherosclerosis and other chronic diseases, and successful treatment and eradication of the organism from tissues would therefore be desirable. The purpose of this study was to assess the effects of C. pneumoniae inoculations on the development of chronic infection and atherosclerotic changes in normocholesterolemic, wild-type mice. We also aimed to elucidate the effects of antibiotic and other treatments on the eradication of chlamydia and on the reduction of the pathologic sequelae induced by these infections.
Female C57BL/6J mice were fed either normal chow when assessing the effects of acute infection, or a diet supplemented with 0.2% cholesterol when evaluating the atherosclerotic changes. Primary or repeated inoculations with C. pneumoniae isolate K7 were given to the mice intranasally, and the effects of treatments with telithromycin, levofloxacin and erythromycin antimicrobial agents and with the phenolic compounds quercetin, luteolin and octyl gallate were evaluated. The following methods were used to measure infection and treatment effects and the presence of chlamydia in tissue: chlamydia culture, PCR and RT-PCR methods, histology of lung, heart and aortic tissue, serologic methods and measurements of aortic contractility responses.
Repeated C. pneumoniae inoculations induced persistent chlamydial DNA and inflammation in lung tissue and development of mouse Hsp60 autoantibodies. Infection was shown to influence aortic endothelial function, and repeated inoculations significantly increased subendothelial lipid accumulation in the aortic sinus area. A flavonoid, luteolin, was shown to effectively decrease the chlamydial load and inflammatory reactions in lung tissue. All antimicrobial agents eradicated the presence of viable chlamydia effectively; however, PCR positivity persisted in lung tissue despite the treatments. Only immediate treatment after each inoculation was able to decrease aortic sinus lipid accumulation.
In conclusion, these data support the role of C. pneumoniae in promoting atherosclerotic development via autoimmune responses and also via direct effects on aortic tissue. Conventional antimicrobial treatments may not effectively eradicate persistent infection, and further studies are warranted to seek for alternative treatment options.
Acta Universitatis Ouluensis. D, Medica
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