Vascular cell responsiveness to Toll‐like receptor ligands in carotid atheroma

Abstract

Acknowledgements: These studies were supported by funding from the British Heart

Diverse Bacteria Promote Macrophage Foam Cell Formation Via Toll-Like Receptor-Dependent Lipid Body Biosynthesis

“…High throughput sequencing of bacterial 16S genes cloned from human atheroma samples has revealed that DNA signatures from a wide variety of bacterial species are present in human atherosclerotic lesions [12][13][14][15][16] . Because these organisms are generally not cultivable from plaques (i.e., they are non-viable), and since many of the identified sequences are derived from common environmental and commensal organisms, their presence in plaques has until now been considered to be largely innocuous; however, the results of the present study suggest for the first time that many, if not most, of these 'innocent bystanders' are capable of promoting the accumulation of cholesterol ester and lipid bodies in macrophages independently of bacterial viability or established modes of pathogenicity.…”

“…A panel of bacteria was selected on the basis of those most frequently reported to be present in human atheroma using 16S gene PCR [12][13][14][15][16] . These included the Gram-negative organisms Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas diminuta and Proteus vulgaris and the Gram-positive organisms Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus salivarius.…”

“…We next examined the potential of a diverse panel of bacteria, representing those most commonly identified in human atheroma [12][13][14][15][16] , to promote lipid accumulation in murine J774 macrophages. Because the quantification of lipid body formation by light microscopy is laborious and potentially open to operator bias, the lipid content of challenged macrophages was measured in these experiments by flow cytometry following staining with the lipophilic fluorescent dye Nile red, as described previously 27) .…”

“…One such example is the bacterium Chlamydia pneumoniae, which has been shown previously to promote lipid body formation in human and murine macrophages [8][9][10] . Early studies of the mechanisms linking infections and atherosclerosis focussed on this organism in particular because it was the first bacteria to be identified in human atherosclerotic lesions 11) ; however, we and others have more recently reported that DNA signatures of a diverse range of bacteria are present in human atheroma [12][13][14][15][16] . These signatures are all but absent from healthy arteries, and are thought to be delivered to plaques within recruited monocytes that have phagocytosed these organisms in the periphery [17][18][19][20][21] .…”

Cultivation of Enterobacter Hormaechei from Human Atherosclerotic Tissue

“…These data suggest the possibility of a polymicrobial origin for atherogenesis 5) . Similarly, 16S PCR identification of bacterial DNA in atheromas revealed the presence of DNA from 17 different bacterial genera 6) ; however, only the culture and characterization of viable clinical isolates from diseased tissue can identify the causative role of bacterial infection in atherosclerotic inflammation.…”