Chlamydia pneumoniae and atherosclerosis: links to the disease process.
Chlamydia pneumoniae is an obligate intracellular prokaryotic human pathogen responsible for a significant portion of atypical pneumonia and associated with a variety of chronic sequelae, the most significant of which is atherosclerosis. The organism is endowed with several attributes that may contribute to the development of atherosclerotic lesions or promote tissue damage at the site of an existing lesion. Two key events that are directly involved in the atherogenic process include the development of foam cells from macrophages and the oxidation of lipoproteins at the site of lesion development. The former process allows for deposition of cholesterol-containing low-density lipoprotein (LDL) and the latter can contribute directly to tissue damage locally. We have hypothesized that C pneumoniae may interact with mononuclear phagocytes in ways that are consistent with the view that this organism contributes to atherosclerotic lesion development. We have demonstrated that the presence of C pneumoniae causes macrophage foam cell formation and lipid oxidation with murine and human cells cocultured in the presence of LDL. In addition, we have provided evidence that implicates 2 putative chlamydial virulence factors in the development of these pathologic processes. Chlamydial lipopolysaccharide has been shown to cause macrophages to develop into foam cells in the presence of LDL, and the 60-kDa chlamydial heat shock protein (cHsp60), a known pathogenesis-inducing protein, has been found to contribute to oxidation of LDL in the presence of macrophages. Work is currently underway to define mechanisms involved in these processes and to further refine the putative role of C pneumoniae in atherogenesis and atherosclerotic lesion development.
Byrne
G I
GI
Department of Medical Microbiology, University of Wisconsin, Madison, USA. gibyrne@facstaff.wisc.edu
Kalayoglu
M V
MV
D001161:Arteriosclerosis / Q000382:microbiology*; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000494:pharmacology; D002690:Chlamydia Infections / Q000150:complications* / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D002788:Cholesterol Esters / Q000096:biosynthesis; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D018834:Chaperonin 60; D002788:Cholesterol Esters; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein