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Role of MyD88-dependent and MyD88-independent signaling in Porphyromonas gingivalis-elicited macrophage foam cell
Y B Shaik-Dasthagirisaheb1, N Huang, M T Baer
1Section of Infectious Diseases, Department of Medicine, Boston University Medical Center, Boston, MA, USA.
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.
Insights
Periodontal disease linked to atherosclerosis involves macrophage foam cell formation. MyD88 and TRIF signaling pathways are crucial in this process, influencing the response to Porphyromonas gingivalis.
Area of Science:
- Immunology
- Cardiovascular Research
- Microbiology
Background:
- Periodontal disease is potentially linked to atherosclerosis and macrophage foam cell formation.
- Toll-like receptors (TLRs) and their signaling molecules, like MyD88, are implicated in both atherosclerosis and host responses to periodontal pathogens such as Porphyromonas gingivalis.
Purpose of the Study:
- To investigate the specific roles of MyD88 and TRIF signaling pathways in macrophage foam cell formation induced by Porphyromonas gingivalis.
Main Methods:
- Mouse bone-marrow-derived macrophages (BMφ) were cultured with human low-density lipoprotein (LDL) and challenged with live or heat-killed P. gingivalis.
- Macrophage foam cell formation was assessed using Oil Red O staining.
- Experiments utilized macrophages from MyD88-knockout and TRIF-deficient (Lps2) mice to elucidate pathway involvement.
- Cytokine production (TNF-α and IL-6) was measured.
Main Results:
- P. gingivalis challenge, in the presence of LDL, led to significant reduction in TNF-α and IL-6 production by BMφ.
- Macrophage foam cell formation occurred irrespective of the timing of bacterial challenge relative to LDL exposure.
- Both live and heat-killed P. gingivalis stimulated foam cell formation.
- MyD88 played a significant role, while TRIF had a minor role in P. gingivalis-induced foam cell formation.
- MyD88 ablation and TRIF status affected P. gingivalis-elicited TNF-α and IL-6 production.
Conclusions:
- Low-density lipoprotein influences the inflammatory response of macrophages to P. gingivalis.
- MyD88 and TRIF are key mediators in the formation of macrophage foam cells in response to P. gingivalis, a critical step in atherosclerosis development.
