Oral Polymicrobial Infection of Integrin b6-/- Mice Demonstrates a Causal Association with Arterial Infection and Inflammation .

I. M. Velsko1, S. Chukkapalli1, M. F. Rivera1, D. Zheng2, A. Lucas2, H. Larjava3, L. Kesavalu1;
1Coll. of Dentistry, Univ. of Florida, Gainesville, FL, 2Coll. of Med., Univ. of Florida, Gainesville, FL, 3Univ. of British Columbia, Vancouver, BC, Canada

Periodontal disease (PD) is an infectious inflammatory disease of the tissues that support the teeth. Although mice are used as a common model of PD, they do not develop the severe symptoms seen in humans. Mice deficient in alpha-v-β6 integrin (itgβ6-/-) develop severe PD, providing an ideal model for human-specific periodontal pathogenic bacteria to colonize and in turn cause widespread disease. Periodontal infection in itgβ6-/- mice may provide a model to study the relationship between PD and systemic vascular disease including atherlosclerosis, a leading cause of morbidity and mortality in North America. We investigated the ability of a microbial consortium of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum to colonize the periodontal pockets of itgβ6-/- mice and examined the local and systemic inflammatory response. Wild-type FVB and itgβ6-/- mice were orally inoculated with four bacterial species (n=12, 9 respectively) or sterile vehicle control (n=12, 7, respectively) for 24 wks, and on euthanasia jaws, sera and organs were collected for analysis. Jaws were examined for gingival inflammation, bone loss, and cytokine profile. Serum antibody response and lipid profile were analyzed. Aortas were collected for plaque histomorphometric analysis and PCR array analysis of gene expression. Splenic T cell profile was determined by cytokine array. Polymicrobial infection was associated with severe bone resorption in infected mice with a strong specific antibody response. Gingiva of infected itgβ6-/- mice demonstrated inflammation and junctional epithelial migration. Th2 cytokines dominated the oral cavity of infected itgβ6-/- mice, and were the predominant cytokines expressed by splenocytes. Aortic gene expression demonstrated significant alterations in specific TLR and NLR pathway genes in infected itgβ6-/- mice not seen in controls. Preliminary aortic histology has demonstrated small areas of plaque growth. Itgβ6-/- mice demonstrate higher susceptibility to periodontal infection, and a greater propensity for systemic spread of infection, and potentially serve as a superior model for studying associations between PD and systemic inflammatory diseases. Supported by R01 DE020820 and F31 DE023492 NIH/NIDCR.