Oral Immunobiology of MCMV-infected Mouse Salivary Glands

MCMV 感染小鼠唾液腺的口腔免疫生物学

• 批准号: 7537438
• 负责人: STEVEN D LONDON
• 金额: $ 32.85万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7537438
• 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; Simplexvirus; 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 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

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.

适当的唾液腺功能对于维持口腔健康和生理健康至关重要。 唾液的功能是湿润口腔组织，作为语言的辅助，作为味觉的重要溶剂，以及作为口腔粘膜的营养成分。 咀嚼润湿剂/润滑剂，对吞咽食物很重要。唾液中含有无机物和有机物 对口腔软组织和牙齿的健康很重要的成分。唾液腺功能障碍 导致唾液分泌减少和/或唾液成分改变 口腔干燥症（Xerostomia）唾液在宿主防御中也起着重要作用，并且是免疫系统的主要贡献者。 宿主对上消化道的先天防御。此外，唾液腺是一个主要的 口腔粘膜免疫系统中的一种成分，赋予口腔粘膜的抗原特异性免疫力。 和粘膜获得性病原体。虽然人们早就知道唾液腺是一个重要的 口腔中的效应器官，唾液腺是否可以作为诱导部位的问题 在免疫反应中的作用还没有得到解决。如果唾液腺是一个诱导部位， 作为效应位点，唾液腺的抗原刺激可能足以诱导对病毒的免疫 和其它病原体甚至在远端粘膜部位。了解唾液腺的免疫生物学 由于基因治疗和组织工程的快速发展， 因为它与唾液腺有关。通过体内基因转移“重新设计”唾液腺的能力， 所得到液体分泌的原位恢复以及利用唾液内分泌途径 全身性基因治疗为更好地了解唾液腺如何分泌提供了额外的理由。 腺免疫与转移基因的表达相互作用，特别是因为转移的基因 基因经常利用重组病毒载体表达。小鼠巨细胞病毒（MCMV） 感染已经用作研究唾液腺免疫的工具。此外，MCMV感染有 已经被用作人类CMV感染的模型一段时间了。人类CMV感染很常见 但在免疫活性健康成人中不会导致显著疾病。然而，在免疫功能低下的 患者（移植受者或艾滋病患者）CMV感染成为严重的并发症和来源 死亡率。因此，了解MCMV感染的免疫反应可以更好地 了解人类CMV感染的发病机制。此外，人类CMV可以传播 通过口腔和呼吸道分泌物以及性传播。这使得调查 对MCMV的粘膜应答，特别是与人类感染相关的粘膜应答。在这个应用程序中，我们有 利用MCMV建立了一种新的唾液腺聚集性感染模型。目标#1将调查 假设唾液腺可以作为一个诱导网站的背景下，共同的粘膜 免疫系统目的#2将研究唾液腺功能性产生的假设 粘膜和全身部位对MCMV感染的保护性免疫。