Treponema denticola Induced Oral and Systemic Changes in ApoEnull Mice

Objectives: Periodontal diseases are complex, multifactorial diseases caused by polymicrobial infections and aggressive immune/inflammatory responses. A distinct pathogenic consortium of Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf) is found in subgingival plaque in human periodontitis.  This study was designed to evaluate the discrete link between T. denticola chronic (24 weeks) oral infection-induced periodontal disease and atherosclerosis in hyperlipidemic ApoE^null mice.

Methods: ApoE^null mice (N=24) were orally infected (8 infections, 4 days/week consecutively) with the oral spirochete T. denticola ATCC 35404 at 10⁹ cells mixed with 4% carboxymethylcellulose. T. denticola infected mice were euthanized at 12 and 24 weeks. Oral plaque samples (PCR), serum antibody response (ELISA), gingival inflammation (Histology, histometry), horizontal alveolar bone resorption (morphometry), and intrabony defects were evaluated (Periodontal disease parameters). Heart, aorta, spleen, liver, lungs, and kidney were evaluated for systemic infection by PCR and aorta was examined for atherosclerotic lesion.

Results: T. denticola genomic DNA was detected in oral plaque samples by PCR indicating T. denticola colonization in oral cavity. Infection elicited significantly higher levels of IgG antibodies and enhanced intrabony defects compared to sham-infected control mice. T. denticola specific genomic DNA, aortic plaque, histology and detection of bacteria by fluorescence in situ hybridization (FISH) are in progress.

Conclusions: This is the first study examining the effect of 24 weeks of chronic T. denticola induced periodontal disease, bacteremia, systemic infection, and atherosclerosis in vivo in proatherogenic ApoE^null mice.