This application is based upon the premise that the innate host response to oral commensal colonization 5 beneficial to the host. In other words, the protective response elicited by the host to oral commensal bacterial colonization in fact contributes to normal periodontal tissue functions with respect to prevention of disease. It is known that clinically healthy periodontal tissue contains a highly orchestrated expression pattern of select innate host defense components that are believed to function in protecting this tissue and the host from pathogens. Studies in germ-free mice have revealed that commensal bacterial colonization of the intestine stimulates host responses that contribute to the ontogeny of the intestine with respect to immune and tissue function. Therefore, we wish to test the hypothesis that: """"""""Commensal oral bacteria contribute to the ontogeny of the innate host response found in clinically healthy periodontal tissue"""""""". We will examine this hypothesis in three Specific Aims.
Specific Aim 1 will compare the periodontal innate post defense status in germ-free and conventionally reared mice to identify those host components regulated by commensal oral bacteria.
This Aim will determine the contribution of commensal bacteria to the ontogeny of the innate host response in the periodontium.
Specific Aim 2 will determine if P. gingivalls, a well-known periopathogen can alter the """"""""beneficial homeostasis"""""""" established between the host and its commensal flora.
n Specific Aim 3 changes in gingival epithelial cell TLR2 and TLR4 expression levels that may alter commensal homeostasis with the host will be determined. Since both microbial composition and innate host response expression patterns are dynamic and likely to change over time these last two Aims are potentially relevant to alterations in oral bacterial I host interactions that may occur with increasing age. ? ? ?
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| Irie, Koichiro; Tomofuji, Takaaki; Ekuni, Daisuke et al. (2015) Impact of Oral Commensal Bacteria on Degradation of Periodontal Connective Tissue in Mice. J Periodontol 86:899-905 |
| Roberts, Frank A; Darveau, Richard P (2015) Microbial protection and virulence in periodontal tissue as a function of polymicrobial communities: symbiosis and dysbiosis. Periodontol 2000 69:18-27 |
| Irie, K; Novince, C M; Darveau, R P (2014) Impact of the Oral Commensal Flora on Alveolar Bone Homeostasis. J Dent Res 93:801-6 |
| Greer, Ara; Zenobia, Camille; Darveau, Richard P (2013) Defensins and LL-37: a review of function in the gingival epithelium. Periodontol 2000 63:67-79 |
| Zenobia, Camille; Luo, Xiao Long; Hashim, Ahmed et al. (2013) Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis. Cell Microbiol 15:1419-26 |
| Hajishengallis, George; Darveau, Richard P; Curtis, Michael A (2012) The keystone-pathogen hypothesis. Nat Rev Microbiol 10:717-25 |
| Darveau, R P; Hajishengallis, G; Curtis, M A (2012) Porphyromonas gingivalis as a potential community activist for disease. J Dent Res 91:816-20 |
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| Coats, Stephen R; Berezow, Alex B; To, Thao T et al. (2011) The lipid A phosphate position determines differential host Toll-like receptor 4 responses to phylogenetically related symbiotic and pathogenic bacteria. Infect Immun 79:203-10 |
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