Persistent Chlamydia pneumoniae infection, inflammation and innate immunity
|Organizations:||University of Oulu, Faculty of Medicine, Institute of Diagnostics, Department of Medical Microbiology
National Institute for Health and Welfare, Department of Child and Adolescent Health an Welfare Unit
|Online Access:||PDF Full Text (PDF, 3.6 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:9789514289965
|Publish Date:|| 2008-12-30
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in the Auditorium of Kastelli Research Centre (Aapistie 1), on January 9th, 2009, at 12 noon
Professor Seppo Nikkari
Docent Mirja Puolakkainen
Chlamydia pneumoniae is an obligatory intracellular pathogen that causes upper and lower respiratory tract infections. Like other Chlamydial species, also C. pneumoniae has a tendency to cause persistent infections, which have been associated with different cardiovascular, neurological, and respiratory diseases. In addition, a few studies have reported an association between C. pneumoniae seropositivity and an elevated body mass index (BMI), and it has been shown that C. pneumoniae is capable of infecting preadipocytes and adipocytes. The main aims of this study were to study if certain gene polymorphisms regulate the serum levels of innate immunity and inflammation proteins, and if the polymorphisms are associated with markers of C. pneumoniae infection; to compare different methods in detection of C pneumoniae in atherosclerotic tissue; and to study if serum levels of chlamydial LPS (cLPS) are associated with BMI.
The serum levels of inflammatory and innate immunity markers, namely interleukin 6 (IL-6), C-reactive protein (CRP), LPS-binding protein (LBP), and soluble CD14, in apparently healthy individuals were found to correlate with each other and possibly be regulated by the polymorphisms of genes important in inflammation and innate immunity. Especially the serum LBP levels may be regulated by the LBP (rs2232618) and toll-like receptor 4 (rs4986790) polymorphisms. The IL-6 (rs1800795) polymorphism was found to be associated with C. pneumoniae antibody positivity.
C. pneumoniae DNA and cLPS could be found from atherosclerotic tissue. A new, cLPS enzyme immunoassay method was developed in this study, and it might provide a standardized, commercial method for the detection of chlamydia in tissue samples, if the sensitivity of the method could be increased e.g. by testing multiple pieces of tissue. In situ hybridization method was found to be complicated by technical problems and the repeatability of polymerase chain reaction was poor.
C. pneumoniae IgG positivity and elevated serum cLPS and CRP levels were associated with an elevated BMI. There was also a strong association between cLPS levels and inflammation as measured by CRP levels. The lack of association between serum total endotoxin activity and BMI implies that the association between infection and an elevated BMI may be specific to certain pathogens.
Acta Universitatis Ouluensis. D, Medica
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