IMR Press / FBL / Volume 13 / Issue 6 / DOI: 10.2741/2822

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Engagement of specific innate immune signaling pathways during Porphyromonas gingivalis induced chronic inflammation and atherosclerosis

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1 Department of Medicine, Boston University School of Medicine, oston, MA 02118
2 Section of Infectious Diseases and Molecular Medicine, Boston University School of Medicine, oston, MA 02118
3 Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118
4 Department of Microbiology, Boston University School of Medicine, Boston, MA 02118

*Author to whom correspondence should be addressed.

Academic Editor: George Hajishengallis

Front. Biosci. (Landmark Ed) 2008, 13(6), 2041–2059;
Published: 1 January 2008

Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. The expression of TLRs are markedly augmented in human atherosclerotic lesions and this occurs preferentially by endothelial cells and macrophages in areas infiltrated with inflammatory cells. Furthermore polymorphisms in the human gene encoding one TLR receptor (TLR4) which attenuates receptor signaling and diminishes the inflammatory response to gram-negative pathogens, is associated with low levels of certain circulating mediators of inflammation and a decreased risk for atherosclerosis in humans. Recent advances have established a fundamental role for inflammation in mediating all stages of atherosclerosis. However, the triggers that initiate and sustain the inflammatory process have not been definitively identified. Although definitive proof of a role of infection contributing to atherogenesis is lacking, multiple investigations have demonstrated that infectious agents evoke cellular and molecular changes supportive of such a role. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen Porphyromonas gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. We have also established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local chronic inflammation versus distant chronic inflammation. We postulate that bacterial infection mediates inflammatory responses that involve specific innate immune pathways in defined host cells. Furthermore, these inflammatory responses can be correlated with atherosclerosis and ultimately thrombotic complications.

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