Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas gingivalis in a mouse model

Abstract

Periodontal disease results from the inflammatory response to bacteria in dental plaque (reviewed in [1]). Although there are well over 300 different bacterial species in the plaque, progression to periodontitis depends not on bacterial load, but on the presence of specific periodontopathic bacteria. The major pathogens identified at the 1996 World Workshop in Periodontics as causative agents are Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Bacteroides forsythus [2]. P. gingivalis has been found in 15% of subjects in an Australian population, the prevalence increasing with increasing pocket depth [3]. In another study, Slots and Ting [4] found that 40-100% of adult periodontitis patients were positive for P. gingivalis. This high occurrence, together with the pathogenic potential of P. gingivalis, has made it a major pathogen of adult periodontitis [5].Immunohistological studies have established that a T cell/macrophage lesion identical to a delayed hypersensitivity 238 Effect of Fusobacterium nucleatum on the T and B cell responses toPorphyromonas gingivalis in a mouse model SUMMARYT cell cytokine profiles and specific serum antibody levels in five groups of BALB/c mice immunized with saline alone, viable Fusobacterium nucleatum ATCC 25586, viable Porphyromonas gingivalis ATCC 33277, F. nucleatum followed by P. gingivalis and P. gingivalis followed by F. nucleatum were determined. Splenic CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma and IL-10 by dual colour flow cytometry and the levels of serum anti-F. nucleatum and anti-P. gingivalis antibodies determined by an ELISA. Both Th1 and Th2 responses were demonstrated by all groups, and while there were slightly lower percentages of cytokine positive T cells in mice injected with F. nucleatum alone compared with the other groups immunized with bacteria, F. nucleatum had no effect on the T cell production of cytokines induced by P. gingivalis in the two groups immunized with both organisms. However, the percentages of cytokine positive CD8 cells were generally significantly higher than those of the CD4 cells. Mice immunized with F. nucleatum alone had high levels of serum anti-F. nucleatum antibodies with very low levels of P. gingivalis antibodies, whereas mice injected with P. gingivalis alone produced anti-P. gingivalis antibodies predominantly. Although the levels of anti-F. nucleatum antibodies in mice injected with F. nucleatum followed by P. gingivalis were the same as in mice immunized with F. nucleatum alone, antibody levels to P. gingivalis were very low. In contrast, mice injected with P. gingivalis followed by F. nucleatum produced equal levels of both anti-P. gingivalis and anti-F. nucleatum antibodies, although at lower levels than the other three groups immunized with bacteria, respectively. Anti-Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Prevotella intermedia serum antibody levels were also determined and found to be negligible. In conclusion, F. nucleatum ...

Fusobacterium nucleatum and Tannerella forsythia Induce Synergistic Alveolar Bone Loss in a Mouse Periodontitis Model

“…The data suggest that F. nucleatum modulates the antibody response of the host to T. forsythia. A similar outcome was reported in a previous study in which a decreased antibody response to P. gingivalis was observed in mice previously immunized with F. nucleatum (15). The low IgG titers to T. forsythia and F. nucleatum in the sham-infected mice (Fig.…”

“…Strikingly, F. nucleatum coinfection led to a dampening of the antibody response to T. forsythia. Although we do not know the reason for this phenomenon, a previous study also observed a dampened antibody response to P. gingivalis following exposure to F. nucleatum (15). It is also likely that F. nucleatum suppresses the expression or the availability of antigenically dominant T. forsythia antigens, a result which causes a reduced bacterium-specific antibody response.…”

“…In vivo, F. nucleatum and T. forsythia dominate the intermediate layers of subgingival biofilms (51). Additionally, F. nucleatum can modulate the inflammatory response of the host to other pathogens (13,15,18,30,46).…”

A novel vaccine targeting Fusobacterium nucleatum against abscesses and halitosis

“…The gamma-irradiation may be an excellent alternative to UV for large-scale bacterial inactivation, since it can penetrate into the deeper layer of bacterial culture [27]. It has been documented that immunization with F. nucleatum did not induce the production of cross-reactive antibodies to other oral micro-organisms [28]. Our results showed that anti- S. mutans serum did not cross-react with F. nucleatum (Fig.…”

Improved periodontal health and cardiovascular risk

“…Serum levels of antibodies to hHSP60, P. gingivalis GroEL and P. gingivalis whole cells were determined using an ELISA technique. 18 Each of the antigens (recombinant hHSP60 (2 lg ⁄ ml), P. gingivalis GroEL (2 lg ⁄ ml), and P. gingivalis ATCC 3277 (1 lg ⁄ ml)) was coated onto 96-well high-binding plates (Maxisorb Immunoplates, Nunc, Roskilde, Denmark). Diluted (1:100) serum samples were added followed by peroxidase-conjugated rabbit anti-human IgG (DAKO, Glostrup, Denmark).…”