DNA-based adaptive immunity protect host from infection-associated periodontal bone resorption via recognition of Porphyromonas gingivalis virulence component.
BACKGROUND
Porphyromonas gingivalis (Pg) is one of a constellation of oral organisms associated with human chronic periodontitis. While adaptive immunity to periodontal pathogen proteins has been investigated and is an important component of periodontal bone resorption, the effect of periodontal pathogen DNA in eliciting systemic and mucosal antibody and modulating immune responses has not been investigated.


METHODS
Rowett rats were locally injected with whole genomic Pg DNA in alum. Escherichia coli (Ec) genomic DNA, Fusobacterium nucleatum (Fn) genomic DNA, and saline/alum injected rats served as controls. After various time points, serum IgG and salivary IgA antibody to Ec, Fn or Pg were detected by ELISA. Serum and salivary antibody reactions with Pg surface antigens were determined by Western blot analyses and the specific antigen was identified by mass spectrometry. Effects of genomic DNA immunization on Pg bacterial colonization and experimental periodontal bone resorption were also evaluated.


RESULTS
Sera from Pg DNA, Ec DNA and Fn DNA-injected rats did not react with Ec or Fn bacteria. Serum IgG antibody levels to Pg and Pg surface extracts were significantly higher in animals immunized with Pg DNA as compared to the control groups. Rats injected with Pg DNA demonstrated a strong serum IgG and salivary IgA antibody reaction solely to Pg fimbrillin (41kDa), the major protein component of Pg fimbriae. In the Pg DNA-immunized group, the numbers of Pg bacteria in oral cavity and the extent of periodontal bone resorption were significantly reduced after Pg infection.


CONCLUSIONS
This study suggests that infected hosts may select specific genes from whole genomic DNA of the periodontal pathogen for transcription and presentation. The results indicate that the unique gene selected can initiate a host protective immune response to the parent bacterium.
The Forsyth Institute, Department of Immunology and Infectious Diseases, 245 First Street, Cambridge, MA, United States. Electronic address: xhan@forsyth.org.
Xiaozhe
X
Han
The Forsyth Institute, Department of Immunology and Infectious Diseases, 245 First Street, Cambridge, MA, United States.
Karen B
KB
LaRosa
The Forsyth Institute, Department of Immunology and Infectious Diseases, 245 First Street, Cambridge, MA, United States.
Toshihisa
T
Kawai
The Forsyth Institute, Department of Immunology and Infectious Diseases, 245 First Street, Cambridge, MA, United States.
Martin A
MA
Taubman
D056704:Adaptive Immunity; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D000818:Animals; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000517:prevention & control; D004269:DNA, Bacterial / Q000276:immunology; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D009055:Mouth / Q000276:immunology / Q000382:microbiology; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012463:Saliva / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014774:Virulence
D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; C063055:fimbrillin; D036781:Fimbriae Proteins
APCs; Bacterial genomic DNA; Bone resorption; ELISA; Ec; Escherichia coli; Fn; Fusobacterium nucleatum; Immune response; LPS; MS; Periodontal disease; Pg; Porphyromonas gingivalis; Vaccine; antigen presenting cells; enzyme-linked immunosorbent assay; lipopolysaccharide; mass spectrometry