title: Role of MyD88-dependent and MyD88-independent signaling in Porphyromonas gingivalis-elicited macrophage foam cell formation.
abstract: Clinical studies and experimental modeling identify a potential link between periodontal disease and periodontal pathogens such as Porphyromonas gingivalis and atherosclerosis and formation of macrophage foam cells. Toll-like receptors and molecules governing their intracellular signaling pathways such as MyD88 play roles in atherosclerosis, as well as host response to P. gingivalis. The aim of this study was to define roles of MyD88 and TRIF during macrophage foam cell formation in response to P. gingivalis. In the presence of human low-density lipoprotein (LDL) mouse bone-marrow-derived macrophages (BMφ) cultured with P. gingivalis responded with significant reduction in tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The BMφ stained strongly with oil red O, regardless of whether bacterial challenge occurred concurrent with or before LDL treatment. Heat-killed P. gingivalis stimulated foam cell formation in a similar way to live bacteria. The BMφ from MyD88-knockout and Lps2 mice revealed a significant role for MyD88, and a minor role for TRIF in P. gingivalis-elicited foam cell formation. Porphyromonas gingivalis-elicited TNF-α and IL-6 were affected by MyD88 ablation and to a lesser extent by TRIF status. These data indicate that LDL affects the TNF-α and IL-6 response of macrophages to P. gingivalis challenge and that MyD88 and TRIF play important roles in P. gingivalis-elicited foam cell formation.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University Medical Center, Boston, MA, USA.
authors.forename: Y B
authors.initials: YB
authors.lastname: Shaik-Dasthagirisaheb
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.forename: M T
authors.initials: MT
authors.lastname: Baer
authors.forename: F C
authors.initials: FC
authors.lastname: Gibson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000818:Animals; D001391:Azo Compounds; D001426:Bacterial Proteins / Q000235:genetics; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D004396:Coloring Agents; D005487:Foam Cells / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D008364:Mannosyltransferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D017354:Point Mutation / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001391:Azo Compounds; D001426:Bacterial Proteins; D004396:Coloring Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D008364:Mannosyltransferases; D053594:Myeloid Differentiation Factor 88; D014409:Tumor Necrosis Factor-alpha; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C422469:LpsB protein, bacteria; C011049:oil red O