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Oral Immunobiology of MCMV-infected Mouse Salivary Glands

MCMV 感染小鼠唾液腺的口腔免疫生物学

基本信息

批准号：
7848284
负责人：
STEVEN D LONDON
金额：
$ 32.54万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2012-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7848284
关键词：
Acinar Cell Acquired Immunodeficiency Syndrome Acute Address Adult Antibodies Antibody Formation Antigens B-Lymphocytes Cells Chronic Complication Cytomegalovirus Cytomegalovirus Infections Cytotoxic T-Lymphocytes Deglutition Disease Distal Effector Cell Endocrine Engineering Epithelium Esthesia Experimental Models Fluids and Secretions Food Functional disorder Gene Transfer Genetic Transcription Gland Herpesviridae Host Defense Human Immediate-Early Genes Immune response Immune system Immunity Immunization Immunobiology Immunocompetent Immunocompromised Host Immunoglobulin A Immunoglobulin G Immunoglobulin M Immunoglobulin-Secreting Cells In Situ Inclusion Bodies Infection Injection of therapeutic agent Lead Leucocytic infiltrate Liver London Lubricants Lymphocyte Lymphoid Tissue Maintenance Mediating Memory Modeling Morbidity - disease rate Mouse Strains Mucosal Immune Responses Mucous Membrane Murid herpesvirus 1 Mus Oral Oral cavity Oral health Organ Output Pathogenesis Pathology Pathway interactions Patients Personal Satisfaction Phase Physiological Plasma Cells Play Population Property Recombinants Research Personnel Role Route Saliva Salivary Salivary Glands Serum Sexual Transmission Simulate Site Solvents Source Speech Spleen Structure of aggregated lymphoid follicle of small intestine Surface T-Lymphocyte Taste Perception Time Tissue Engineering Tissues Tooth structure Transplant Recipients Upper digestive tract structure Viral Viral Antibodies Viral Vector Virus Virus Diseases Wetting Agents Xerostomia cell mediated immune response cytokine cytotoxic cytotoxicity differentiated B cell gene therapy in vivo interest intraperitoneal lymph nodes migration mortality mucosal site oral tissue pathogen precursor cell programs respiratory response restoration saliva function soft tissue therapeutic gene tissue culture tool transmission process

项目摘要

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 contains inorganic and organic components important for the health of the oral soft tissues and the teeth. Salivary gland dysfunction resulting in diminished salivary output and/or altered salivary composition results in the subjective sensation of dry mouth (xerostomia). Saliva also plays an important role in host defense and is a major contributor of the innate host defense of the upper gastrointestinal tract. In addition, 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. Although it has long been known that the salivary gland is an important effector organ in the oral cavity, the issue of whether the salivary gland can function as an inductive site during an immune response has not been addressed. If the salivary gland is an inductive site in addition to an effector site, antigenic stimulation of the salivary gland may be sufficient to induce immunity to viruses and other pathogens even at distal mucosal 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 utilize 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 immunocompetent healthy adults. However, in immunocompromised 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 application, we have developed a new model of focused salivary gland infection utilizing MCMV. Aim #1 will investigate the hypothesis that the salivary gland can function as an inductive site in the context of the common mucosal immune system. Aim #2 will investigate the hypothesis that the salivary gland generates functionally protective immunity to MCMV infection at both mucosal and systemic sites.

正常的唾液腺功能对维持口腔健康和生理健康至关重要。