Proper salivary gland function is critical for the maintenance of oral health and physiological well-being. Saliva functions to moisten the oral tissues as an aid for speech, as a solvent important for taste, and as a masticatory wetting agent/lubricant important in swallowing food. Saliva also plays an important role in host defense and is a major contributor of the innate host defense of the upper gastrointestinal tract. The salivary glands are a major component in the mucosal immune system of the oral cavity that confers antigen- specific immunity to oral and mucosally-acquired pathogens. We demonstrated that the salivary gland can act as a mucosal inductive site in addition to an effector site and tha antigenic stimulation of the salivary gland is sufficient to induce immunity at proximal and distal mucosal sites as well as systemic sites. Understanding the immunobiology of the salivary glands is also of particular interest because of rapidly developing progress in gene therapy and tissue engineering as it relates to the salivary gland. The ability to re-engineer the salivary gland via gene transfer in vivo with the resultant in situ restoration of fluid secretion and to utlize salivary endocrine secretory pathways for systemic gene therapeutics provides additional reason for gaining a better understanding of how salivary gland immunity interacts with the expression of transferred gene(s), especially because the transferred gene(s) are frequently expressed utilizing recombinant viral vectors. Murine cytomegalovirus (MCMV) infections have served as a tool for investigating salivary gland immunity. In addition, MCMV infections have already been used for some time as models for human CMV infection. Human CMV infections are common but do not lead to significant disease in immune-competent healthy adults. Nevertheless, in immune-compromised patients (transplant recipients or AIDS patients) CMV infection becomes a serious complication and source of mortality. Therefore, understanding the immune responses to MCMV infections can lead to a better understanding of the pathogenesis of CMV infections in humans. In addition, human CMV can be spread through oral and respiratory secretions and through sexual transmission. This makes investigating the mucosal responses to MCMV, in particular, relevant to infection in humans. In this proposal we will utilize the MCMV model to extend our proof of concept that salivary gland vaccination in particular cannulation of the parotid salivary gland, could be an important new clinical route for mucosal vaccines. This project is ideally suited for a short-term summer exposure to research of interest to the dental student that can easily be expanded over the course of the academic year. We expect that the outcomes of these studies will greatly add to our understanding of salivary gland induced mucosal immunity. The award of this AREA grant will meet the goals of student research at the School of Dental Medicine by fostering scholarship and critical thinking skills, by adding to the body of scientific knowledge, and by facilitating recruitment of students into academic, dental research careers.
The proposed research is relevant to public health because effective immunization strategies are necessary to reduce the burden of disease from pathogens that initiate their infectious processes at mucosal surfaces. Conventional routes of immunization for mucosal surfaces include oral ingestion of vaccines and, more recently, administration of vaccines to the upper respiratory tract through administration via a nasal spray technique. We have developed a new model of focused salivary gland immunization that has allowed us to determine that the salivary gland functions as an inductive site in the context of the common mucosal immune system. This model has the potential to be further developed into a strategy for the induction of protective mucosal immune response to a number of mucosal pathogens including viruses and bacteria. The purpose of the AREA grant program is to stimulate research in educational institutions like Stony Brook University School of Dental Medicine. The goals of student research at the School of Dental Medicine are to foster scholarship and critical thinking skills, to add to the body of scientific knowledge, and to faciliate recruitment of students into academic, dental research careers. The award of this AREA grant will assist the school in meeting these goals.
