Genetic Control of Susceptibility to<i>Porphyromonas gingivalis</i>-Induced Alveolar Bone Loss in Mice

Baker, Pamela J.; Dixon, Mark; Roopenian, Derry C.

doi:10.1128/iai.68.10.5864-5868.2000

Cited by 146 publications

(208 citation statements)

References 29 publications

(31 reference statements)

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“…These data demonstrate that increased alveolar bone loss in MP/PMN-specific Stat3-deficient mice is dependent on P. gingivalis infection, and suggests that MP and/or PMNs are key effector cells of IL-10 in suppression of P. gingivalisinduced alveolar bone loss. The lack of bone loss in the other groups is consistent with a previous report that the C57BL/6J wild-type mouse is resistant to P. gingivalis-induced alveolar bone loss (31).…”

Section: The Mp/pmn-specific Stat3-deficient Mouse Is Susceptible To supporting

confidence: 81%

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Sasaki¹,

Suzuki

Kent

et al. 2008

The Journal of Immunology

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Periodontal disease is a chronic inflammatory disease in the oral cavity, which culminates in alveolar bone loss. Porphyromonas gingivalis is a consensus periodontal pathogen that has been implicated in adult forms of periodontitis. We previously demonstrated that IL-10-deficient mice exhibit a hyperinflammatory phenotype and are highly susceptible to P. gingivalis-induced periodontitis, indicating an important anti-inflammatory effect of IL-10 in suppressing bone loss. In this study, we analyzed the pathway(s) by which IL-10 deficiency leads to severe P. gingivalis-induced periodontitis. Because Stat3 is essential in IL-10 signaling, immune cell-specific Stat3-deficient mice were subjected to P. gingivalis infection to identify the key IL-10-responsive cells in preventing periodontitis. Myeloid cell-specific Stat3-deficient mice exhibited increased periodontal bone loss (p < 0.001), whereas T cell- and B cell-specific Stat3 mice were resistant, suggesting that macrophages (MP) and/or polymorphonuclear leukocytes are the key target cells normally suppressed by IL-10. Myeloid cell-specific Stat3-deficient mice exhibited elevated gingival CD40L gene expression in vivo compared with wild-type controls (p < 0.01), and Stat3-deficient MPs exhibited vigorous P. gingivalis-stimulated IL-12 production in vitro and induced elevated Ag-specific T cell proliferation compared with wild-type MPs (p < 0.01). Of importance, both IL-12p40/IL-10 and T cell/IL-10 double-deficient mice were resistant to P. gingivalis-induced periodontitis, demonstrating roles for both IL-12p40 and T cells in pathogenesis in a hyperinflammatory model of disease. These data demonstrate that P. gingivalis-induced periodontitis in IL-10-deficient mice is dependent upon IL-12p40-mediated proinflammatory T cell responses.

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Section: The Mp/pmn-specific Stat3-deficient Mouse Is Susceptible To supporting

confidence: 81%

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Sasaki¹,

Suzuki

Kent

et al. 2008

The Journal of Immunology

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“…Using a validated model of mouse periodontitis (Baker et al, 2000), we demonstrated that CR3 blockade inhibits the ability of P. gingivalis to persist in the mouse host and to induce periodontal bone loss (Fig. 5B).…”

Section: In Vivo Evidence For Cr3 Exploitation By P Gingivalis and Imentioning

confidence: 94%

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Hajishengallis

Wang²,

Liang³

et al. 2008

Advances in Experimental Medicine and Biology

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The capacity of certain pathogens to exploit innate immune receptors enables them to undermine immune clearance and persist in their host, often causing disease. Here we review subversive interactions of Porphyromonas gingivalis, a major periodontal pathogen, with the complement receptor-3 (CR3; CD11b/CD18) in monocytes/macrophages. Through its cell surface fimbriae, P. gingivalis stimulates Toll-like receptor-2 (TLR2) inside-out signaling which induces the highaffinity conformation of CR3. Although this activates CR3-dependent monocyte adhesion and transendothelial migration, P. gingivalis has co-opted this TLR2 proadhesive pathway for CR3 binding and intracellular entry. In CR3-deficient macrophages, the internalization of P. gingivalis is reduced 2-fold but its ability to survive intracellularly is reduced 1000-fold, indicating that CR3 is exploited by the pathogen as a relatively safe portal of entry. The interaction of P. gingivalis fimbriae with CR3 additionally inhibits production of bioactive (p70) interleukin-12, which mediates immune clearance. In vivo blockade of CR3 leads to reduced persistence of P. gingivalis in the mouse host and diminished ability to cause periodontal bone loss, the hallmark of periodontal disease. Strikingly, the ability of P. gingivalis to interact with and exploit CR3 depends upon quantitatively minor components (FimCDE) of its fimbrial structure, which predominantly consists of polymerized fimbrillin (FimA). Indeed, isogenic mutants lacking FimCDE but expressing FimA are dramatically less persistent and virulent than the wild-type organism both in vitro and in vivo. This model of immune evasion through CR3 exploitation by P. gingivalis supports the concept that pathogens evolved to manipulate innate immune function for promoting their adaptive fitness.

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“…Both mice and rabbits have been previously used to examine various aspects of CD. Although both models have their own limitations, the murine model has the advantage of also being used as a periodontitis model system (41). Thus, it is theoretically possible to induce varying levels of periodontitis in mice for assessment of subsequent CD pathology.…”

Section: Animal Models As Tools To Examine the Periodontitiscardiovasmentioning

confidence: 99%

Periodontopathic Bacteria and Their Potential Involvement in Atherosclerosis

Kuramitsu

2002

Int J Oral-Med Sci

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Genetic Control of Susceptibility toPorphyromonas gingivalis-Induced Alveolar Bone Loss in Mice

Cited by 146 publications

References 29 publications

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Periodontopathic Bacteria and Their Potential Involvement in Atherosclerosis

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