Chlamydia pneumoniae--induced macrophage foam cell formation is mediated by Toll-like receptor 2.
Chlamydia pneumoniae induces macrophage foam cell formation, a hallmark of early atherosclerosis, in the presence of low-density lipoprotein (LDL). This study examined the role that Toll-like receptor 2 (TLR2) and TLR4 may play in pathogen-induced foam cell formation. Murine macrophage RAW 264.7 cells either infected with C. pneumoniae or treated with the TLR4 ligand E. coli lipopolysaccharide (LPS) or the TLR2 ligand Pam(3)-Cys-Ala-Gly-OH (Pam) became Oil Red O-stained foam cells and showed increased cholesteryl ester (CE) content when cocultured with LDL. In macrophages from TLR2(-/-) mice, foam cells were induced by Escherichia coli LPS but not by C. pneumoniae or Pam. Conversely, C. pneumoniae or Pam, but not E. coli LPS, induced foam cells in the TLR4-deficient GG2EE macrophage cell line, suggesting that C. pneumoniae elicits foam cell formation predominantly via TLR2. Enhancing cholesterol efflux using the liver X receptor (LXR) agonist GW3965 significantly decreased the CE content of cells exposed to each of the three TLR ligands (C. pneumoniae, Pam, and E. coli LPS). Overall, our results suggest that activation of the LXR signaling pathway may affect potentially atherogenic processes modulated by the TLR ligands.
Cao
Fei
F
Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Castrillo
Antonio
A
Tontonoz
Peter
P
Re
Fabio
F
Byrne
Gerald I
GI
D000818:Animals; D001565:Benzoates / Q000378:metabolism; D001596:Benzylamines / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000473:pathology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D002788:Cholesterol Esters / Q000032:analysis; D004268:DNA-Binding Proteins / Q000819:agonists; D005487:Foam Cells / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D000071518:Liver X Receptors; D008264:Macrophages / Q000737:chemistry / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology
D001565:Benzoates; D001596:Benzylamines; D002788:Cholesterol Esters; D004268:DNA-Binding Proteins; C473027:GW 3965; D008070:Lipopolysaccharides; D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C061110:N-palmitoyl-5,6-dipalmitoylcysteinyl-alanyl-glycine