ONTOGENY OF INNATE IMMUNE RESPONSES AT MUCOSAL SURFACES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The hallmark of the vertebrate immune system is its ability to maintain an equilibrium between reactivity and quiescence of responses, while geared to respond and adapt rapidly to noxious and potentially lethal challenge. The system must recognize the challenge, develop and express a response to control the challenge, and terminate the reaction in regulating the response. These reactions are the responsibility of components of innate immunity that include cellular receptors and biomolecules at mucosal surfaces and within the systemic circulation. Due to the complexity of the microbial challenge in the oral cavity, it is clear that the innate immune system must play a crucial role in regulating host responses to the commensal microbiota. This proposal engages a collaborative relationship to enable determination of these responses in a human-like model of oral infection and inflammation: (1) This proposal will focus on the use of a nonhuman primate (rhesus) model of periodontal infection and inflammation. It is built upon a unique resource, the Caribbean Primate Research Center (CPRC); (2) This proposal is a collaborative relationship between investigators at the University of Kentucky, the CPRC, and the University of Puerto Rico Dental School; (3) This proposal will provide novel information on innate immunity in cross-sectional studies related to age using various cohorts from young to aged animals, and related to the expression of periodontitis; and, (4) Using the nonhuman primate model of periodontal infection and disease, we will determine longitudinal changes in innate immune responses througout age of development of the individual, specifically related to the initiation, progression, and resolution of the disease process. This model provides for a controlled study of these processes that cannot be accomplished in humans, but provides a human-like model of infection, disease and host responses. The General Hypothesis for the project is that "Innate immune response components in gingival tissues vary with age and periodontal disease expression." This will enable the identification of crucial innate immune molecular events that contribute to gingival homeostasis. The studies proposed in this application will use an innovative strategy in 2 Specific Aims to interface a nonhuman primate model of periodontitis, with microarray gene expression technology to address these critical questions regarding the characteristics and ontogeny of innate responses in the oral cavity.