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Porphyromonas gingivalis virulence in mice: induction of immunity to bacterial components
L Kesavalu1, J L Ebersole, R L Machen
1Department of Periodontics, University of Texas Health Science Center, San Antonio 78284.
Abstract:
Selected cell envelope components of Porphyromonas gingivalis were tested in a BALB/c mouse model in an attempt to elucidate further the outer membrane components of this putative oral pathogen that might be considered as virulence factors in host tissue destruction. Lipopolysaccharide (LPS), outer membrane, and outer membrane vesicles of P. gingivalis W50, ATCC 53977, and ATCC 33277 were selected to examine an immunological approach for interference with progressing tissue destruction. Mice were actively immunized with heat-killed (H-K) or Formalin-killed (F-K) whole cells or with the outer membrane fraction, LPS, or outer membrane vesicles of the invasive strain P. gingivalis W50. The induction of invasive spreading lesions with tissue destruction and lethality were compared among different immunization groups in normal, dexamethasone-treated (dexamethasone alters neutrophil function at the inflammatory site), and galactosamine-sensitized (galactosamine sensitization increases endotoxin sensitivity) mice after challenge infection with the homologous strain (W50) and heterologous strains (ATCC 53977 and ATCC 33277). Enzyme-linked immunosorbent assay analyses revealed significantly elevated immunoglobulin G and M antibody responses after immunization with H-K or F-K cells or the outer membrane fraction compared with those of nonimmunized mice. The killed whole-cell vaccines provided significantly greater protection against challenge infection in normal mice (decreased lesion size and death) than did either the outer membrane fraction or LPS immunization. The lesion development observed in dexamethasone-pretreated mice was significantly enhanced compared with that of normal mice after challenge with P. gingivalis. Immunization with P. gingivalis W50 provided less protection against heterologous challenge infection with P. gingivalis ATCC 53977; however, some species-specific antigens were recognized and induced protective immunity. Only viable P. gingivalis induced a spreading lesion in normal, dexamethasone-treated, or galactosamine-sensitized mice; F-K or H-K bacteria did not induce lesions. The F-K and outer membrane vesicle immunization offered greater protection from lesion induction than did the H-K immunogen after challenge infection simultaneous with galactosamine sensitization. The H-K cell challenge with galactosamine sensitization produced 100% mortality without lesion induction, suggesting that LPS or LPS-associated outer membrane molecules were functioning like endotoxin. Likewise, P. gingivalis W50 LPS (1 micrograms per animal) administered intravenously produced 80% mortality in galactosamine-sensitized mice. In contrast to the effects of immunization on lesion development, immunization with H-K or F-K cells or LPS provided no protection against intravenous challenge with LPS; 100% of the mice died from acute endotoxin toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
Insights
Killed whole cells of Porphyromonas gingivalis provided better protection against infection than outer membrane components. Immunization strategies targeting specific antigens may offer protective immunity against this oral pathogen.
Area of Science:
- Microbiology
- Immunology
- Periodontal Disease Pathogenesis
Background:
- Porphyromonas gingivalis is an oral bacterium implicated in periodontal disease and host tissue destruction.
- Understanding the virulence factors of P. gingivalis, particularly outer membrane components, is crucial for developing effective interventions.
- Investigating immunological approaches to interfere with P. gingivalis-mediated tissue damage is a key research area.
Purpose of the Study:
- To elucidate the role of P. gingivalis outer membrane components as virulence factors in host tissue destruction.
- To evaluate the efficacy of different P. gingivalis cell envelope components as vaccine candidates.
- To assess the protective immunity induced by various immunization strategies against P. gingivalis challenge infections.
Main Methods:
- BALB/c mice were immunized with heat-killed (H-K) or formalin-killed (F-K) whole cells, outer membrane fractions, lipopolysaccharide (LPS), or outer membrane vesicles of P. gingivalis.
- Mice were challenged with homologous and heterologous strains of P. gingivalis under normal, dexamethasone-treated, or galactosamine-sensitized conditions.
- Lesion development, tissue destruction, lethality, and antibody responses (IgG, IgM) were assessed using enzyme-linked immunosorbent assays (ELISA).
Main Results:
- Immunization with H-K or F-K whole cells conferred significantly greater protection against P. gingivalis challenge in normal mice compared to outer membrane fractions or LPS.
- Dexamethasone treatment enhanced lesion development, while galactosamine sensitization increased susceptibility to endotoxin toxicity from P. gingivalis LPS.
- F-K and outer membrane vesicle immunization provided better protection against lesion induction than H-K immunogen in galactosamine-sensitized mice.
Conclusions:
- Killed whole-cell vaccines of P. gingivalis are more effective in preventing infection-induced tissue destruction than isolated outer membrane components.
- P. gingivalis LPS acts as an endotoxin, causing significant mortality in sensitized mice, independent of immunization against cellular components.
- Targeting specific species-associated antigens may induce protective immunity, but whole-cell vaccines offer broader protection against P. gingivalis virulence.