Chlamydia pneumoniaeand atherosclerosis

Abstract

SummaryExposure to Chlamydia pneumoniae is extremely common, and respiratory infections occur repeatedly among most people. Strong associations exist between C. pneumoniae infection and atherosclerosis as demonstrated by: (i) sero-epidemiological studies showing that patients with cardiovascular disease have higher titres of anti-C. pneumoniae antibodies compared with control patients; (ii) detection of the organism within atherosclerotic lesions, but not in adjacent normal tissue by immunohistochemistry, polymerase chain reaction and electron microscopy and by culturing the organism from lesions; and (iii) showing that C. pneumoniae can either initiate lesion development or cause exacerbation of lesions in rabbit and mouse animal models respectively. The association of this organism with atherosclerosis has also provided sufficient impetus to conduct a variety of human secondary prevention antibiotic treatment trials. The results of these studies have been mixed and, thus far, no clear long-lasting benefit has emerged from these types of investigations. Studies of C. pneumoniae pathogenesis have shown that the organism can infect many cell types associated with both respiratory and cardiovascular sites, including lung epithelium and resident alveolar macrophages, circulating monocytes, arterial smooth muscle cells and vascular endothelium. Infected cells have been shown to exhibit characteristics associated with the development of cardiovascular disease (e.g. secretion of proinflammatory cytokines and procoagulants by infected endothelial cells and foam cell formation by infected macrophages). More detailed analysis of C. pneumoniae pathogenesis has been aided by the availability of genomic sequence information. Genomic and proteomic analyses of C. pneumoniae infections in relevant cell types will help to define the pathogenic potential of the organism in both respiratory and cardiovascular disease.

R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells

“…Since there is ample evidence that MC [56], TLR [57] and infectious agents [58,59] play a crucial role in allergic, inflammatory and chronic disorders, we expect that MC-derived cytokines such as TNF-a and IL-6 induced by R-form LPS contribute to the development of these pathologies. In contrast, the cytokine responses of MC to R-form LPS under physiological conditions are very likely beneficial.…”

GroEL1, a Heat Shock Protein 60 of Chlamydia pneumoniae, Induces Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Expression in Endothelial Cells and Enhances Atherogenesis in Hypercholesterolemic Rabbits

“…The role of C. pneumoniae infection in the pathogenesis of atherosclerosis remains controversial (21)(22)(23)(24). Meta-analyses of randomized clinical trials of antibiotic therapy for secondary prevention of coronary heart disease did not show any benefit (25, 26).…”

MyD88 Is Pivotal for the Early Inflammatory Response and Subsequent Bacterial Clearance and Survival in a Mouse Model of Chlamydia pneumoniae Pneumonia

“…Within this family Chlamydia pneumoniae is in particular clinically important, not only because it has a worldwide distribution and is responsible for about 10% of community-acquired pneumonia and 5% of sinusitis and bronchitis, but also because it has been strongly implicated as a major contributor to vascular diseases such as atherosclerosis (2)(3)(4) and chronic lung disease such as asthma (5).…”