Cellular Microbiology of Chlamydia pneumoniae

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DESCRIPTION (provided by applicant): Atherosclerosis has been associated with infection by the bacterial pathogen Chlamydia pneumoniae. The broad, long-term goal of the proposed studies is to define the mechanisms of C. pneumoniae pathogenesis that promote coronary artery disease. The research focus of this application is the molecular characterization of C. pneumoniae interactions with mammalian host cells during acute and persistent infection. The hypothesis is that C. pneumoniae produce components that elicit responses by the host cell and it is the consequent host cell responses including proinflammatory chemokines, growth factors and coagulation factors that mediate pathogenesis and arterial disease. The important role of persistent infection, characteristic of chlamydial infections, on cellular responses and staging the focal environment for chronic inflammation and consequent tissue damage will be evaluated. The significance of these studies is the identification of the cellular mediators of pathogenesis and the chlamydial products that elicit these responses thereby informing new approaches for control and diagnosis by identifying novel targets for diagnostic detection and vaccine or chemical intervention. The specific aims will be investigated utilizing oligonucleotide and DNA array formats to measure changes in transcription in parallel for approximately 30,000 human genes and 1,100 C. pneumoniae genes. Human cellular responses will be tested in cells known to be infected by chlamydia in diseased arterial tissues including vascular endothelial cells, smooth muscle cells and macrophages. The specific aims are: 1) Determine the spectrum of cellular responses to infection by C. pneumoniae. 2) Validate the protein expression of C. pneumoniae-induced changes in host cell gene transcription. 3) Characterize gene expression profiles for C. pneumoniae during persistent infection and during growth in different cell types. 4) Identify chlamydial products and test persistently-expressed C. pneumoniae gene products for their ability to induce host cell responses.