Porphyromonas gingivalis fimbriae are pro-inflammatory but do not play a prominent role in the innate immune response to P. gingivalis

The fimA gene encodes the major fimbrial protein of Porphyromonas gingivalis. It has been shown to stimulate adhesion to salivary proteins and other bacteria. It is also thought to play a major role in invading and stimulating host cells. To determine whether the fimA gene represents one of the principal molecules of P. gingivalis that induces inflammation, we tested purified FimA protein and a mutant P. gingivalis (DPG3) that lacks the fimA gene versus wild-type (WT) P. gingivalis. When injected into connective tissue of the scalp, purified FimA protein induced TNF-α and MIP-2 expression confirming that it is pro-inflammatory. WT P. gingivalis induced TNF-α expression and recruitment of PMNs in the same model. However, DPG3 P. gingivalis stimulated TNF expression and PMN recruitment to the same extent. The latter was consistent with similar induction of the chemokine MIP-2. Similar results were obtained with diabetic mice that have a more prolonged inflammatory response to bacterial stimulation. These results indicate that FimA is a potent inducer of inflammatory cytokine expression but, in the context of P. gingivalis infection, it is not a principal stimulator of the innate host response.

[1]  D. Graves,et al.  Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation. , 2004, The Journal of investigative dermatology.

[2]  C. Cutler,et al.  Fimbriated Porphyromonas gingivalis Is More Efficient than Fimbria-Deficient P. gingivalis in Entering Human Dendritic Cells In Vitro and Induces an Inflammatory Th1 Effector Response , 2004, Infection and Immunity.

[3]  R. Genco,et al.  Downregulation of the DNA-Binding Activity of Nuclear Factor-κB p65 Subunit in Porphyromonas gingivalis Fimbria-Induced Tolerance , 2004, Infection and Immunity.

[4]  T. Ogawa,et al.  Binding of Porphyromonas gingivalis fimbriae to Treponema denticola dentilisin. , 2003, FEMS microbiology letters.

[5]  Ozlem Yilmaz,et al.  Gingival epithelial cell signalling and cytoskeletal responses to Porphyromonas gingivalis invasion. , 2003, Microbiology.

[6]  S. Hamada,et al.  Identification of a new variant of fimA gene of Porphyromonas gingivalis and its distribution in adults and disabled populations with periodontitis. , 2002, Journal of periodontal research.

[7]  K. Ohura,et al.  Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. , 2002, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[8]  R. Genco,et al.  Dependence of Bacterial Protein Adhesins on Toll-Like Receptors for Proinflammatory Cytokine Induction , 2002, Clinical and Vaccine Immunology.

[9]  F. C. Gibson,et al.  Fimbria-Dependent Activation of Cell Adhesion Molecule Expression in Porphyromonas gingivalis-Infected Endothelial Cells , 2002, Infection and Immunity.

[10]  D. Graves,et al.  Tumor Necrosis Factor Modulates Fibroblast Apoptosis, PMN Recruitment, and Osteoclast Formation in Response to P. gingivalis Infection , 2001, Journal of dental research.

[11]  H. Anan,et al.  Mixed infection of Porphyromonas gingivalis and Bacteroides forsythus in a murine abscess model: involvement of gingipains in a synergistic effect. , 2001, Journal of periodontal research.

[12]  J. Potempa,et al.  Mechanisms Mediating Porphyromonas gingivalis Gingipain RgpA-Induced Oral Mucosa Inflammation In Vivo , 2001, Infection and Immunity.

[13]  D. Graves,et al.  Interleukin-1 and Tumor Necrosis Factor Activities Partially Account for Calvarial Bone Resorption Induced by Local Injection of Lipopolysaccharide , 1999, Infection and Immunity.

[14]  S. Socransky,et al.  Ecological considerations in the treatment of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis periodontal infections. , 1999, Periodontology 2000.

[15]  Yanling Jiang,et al.  Bacterium-Dependent Induction of Cytokines in Mononuclear Cells and Their Pathologic Consequences In Vivo , 1999, Infection and Immunity.

[16]  D. Graves.  The potential role of chemokines and inflammatory cytokines in periodontal disease progression. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  R. G. Deshpande,et al.  Invasion of Aortic and Heart Endothelial Cells byPorphyromonas gingivalis , 1998, Infection and Immunity.

[18]  L. Kesavalu,et al.  Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin , 1998, Infection and Immunity.

[19]  S. Amar,et al.  Strain-Dependent Activation of Monocytes and Inflammatory Macrophages by Lipopolysaccharide ofPorphyromonas gingivalis , 1998, Infection and Immunity.

[20]  S. Hamada,et al.  The importance of fimbriae in the virulence and ecology of some oral bacteria. , 1998, Oral microbiology and immunology.

[21]  S. Socransky,et al.  Microbial complexes in subgingival plaque. , 1998, Journal of clinical periodontology.

[22]  R. Genco,et al.  A role for fimbriae in Porphyromonas gingivalis invasion of oral epithelial cells , 1997, Infection and immunity.

[23]  C. M. Belton,et al.  Role of fimbriae in Porphyromonas gingivalis invasion of gingival epithelial cells , 1997, Infection and immunity.

[24]  P. A. Raj,et al.  Structural domains of Porphyromonas gingivalis recombinant fimbrillin that mediate binding to salivary proline-rich protein and statherin , 1996, Infection and immunity.

[25]  M. Hayashi,et al.  In vivo induction of apoptosis and immune responses in mice by administration of lipopolysaccharide from Porphyromonas gingivalis , 1996, Infection and immunity.

[26]  R. Genco,et al.  Purification of major fimbrial proteins of Porphyromonas gingivalis. , 1995, Protein expression and purification.

[27]  C. Sasakawa,et al.  Construction and characterization of a fimA mutant of Porphyromonas gingivalis , 1994, Infection and immunity.

[28]  S. Amar,et al.  Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes: dependence on serum and CD14 receptor. , 1994, Oral microbiology and immunology.

[29]  T. Ogawa,et al.  Porphyromonas gingivalis fimbriae and their synthetic peptides induce proinflammatory cytokines in human peripheral blood monocyte cultures. , 1994, FEMS microbiology letters.

[30]  J. G. Fisher,et al.  Inactivation of the Porphyromonas gingivalis fimA gene blocks periodontal damage in gnotobiotic rats , 1994, Journal of bacteriology.

[31]  A. Tanner,et al.  Oral and dental infections with anaerobic bacteria: clinical features, predominant pathogens, and treatment. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  R. Genco,et al.  Immunization with Porphyromonas (Bacteroides) gingivalis fimbriae protects against periodontal destruction , 1992, Infection and immunity.

[33]  R. Genco.  Host Responses in Periodontal Diseases: Current Concepts. , 1992, Journal of periodontology.

[34]  T. Ogawa,et al.  Immunobiological activities of synthetic peptide segments of fimbrial protein from Porphyromonas gingivalis. , 1991, Biochemical and biophysical research communications.

[35]  S. Holt,et al.  Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. , 1988, Science.