Decreased Expression of Liver X Receptor-α in Macrophages Infected with <i>Chlamydia pneumoniae</i> in Human Atherosclerotic Arteries in situ

Abstract

In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells.

Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

“…Interestingly, several microorganisms have been observed to trigger various intracellular pathways associated with M1 polarization, such as Listeria monocytogenes , Chlamydia ssp., and Salmonella typhimurium [ 121 ]. In fact, C. pneumoniae [ 122 , 123 ], Helicobacter pylori [ 124 ], and Cytomegalovirus [ 125 ] have been identified in the atherosclerotic lesions, where they may promote polarization of the local macrophages towards the M1 phenotype and upregulate M1-related genes like TNF- α , IL-6, IL-1 β , CCL2, CCL5, and CXCL8 [ 126 ].…”

Liver X receptors contribute to periodontal pathogen‐elicited inflammation and oral bone loss

“…However, LXR‐deficient mice were more resistant to infection with the protozoan Leishmania chagasi / infantum (Bruhn et al ., ). In vitro Chlamydia pneumoniae infection had no effect on LXR gene expression; yet, when investigated in vivo , C. pneumoniae stimulated a 2.2‐fold reduction in LXRα gene expression in aortic cells of hyperlipidemic mice (Bobryshev et al ., ). LXRs have also been implicated in host response to viruses including human immunodeficiency virus and hepatitis B virus (Kim et al ., ; Hanley et al ., ; Renga et al ., ), as well as to bacterial LPS (Wang et al ., ; Myhre et al ., ).…”

Putative biofilm-forming organisms in the human vasculature: expanded and review of the literature

“…The presence of Cytomegalovirus has been reported in atherosclerotic plaques in 105 patients with acute coronary syndromes [110]. A cell biology potential of macrophages to transition to foam cells has been suggested whereby macrophages have reduced liver X receptor-α in atherosclerotic arteries when infected with Chlamydia pneumoniae [111]. In further support, Chlamydia pneumoniae antigens have been detected in coronary atheroma [112] as well as early atherosclerotic plaques [113].…”