Oral Macrophage Function in the Context of Periodontal Disease and HIV Infection

牙周病和 HIV 感染背景下的口腔巨噬细胞功能

• 批准号: 8739537
• 负责人: FRANK C GIBSON
• 金额: $ 62.14万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-25 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8739537
• 关键词: Anaerobic Bacteria; Antigen Presentation Pathway; Biochemical Pathway; Cell model; Cells; Chronic; Clinical; Complement; Complex; Dental Care; Disease; Epigenetic Process; Event; Genetic Transcription; Goals; HIV; HIV Infections; HIV-1; Healthcare; Highly Active Antiretroviral Therapy; Homeostasis; Human; Immunity; Immunosuppression; In Vitro; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Lead; Life Expectancy; Molecular Target; Mouth Diseases; Oral; Oral cavity; Oropharyngeal; Palatine Tonsil; Pathogenesis; Patients; Periodontal Diseases; Phenotype; Play; Population Heterogeneity; Porphyromonas gingivalis; Receptor Protein-Tyrosine Kinases; Regulation; Reporting; Resistance; Role; Saliva; Sampling; Signal Transduction; Source; Tissues; Tonsil; Tooth structure; Virus; Virus Replication; cohort; cytokine; experience; innate immune function; insight; macrophage; novel; oral bacteria; oral pathogen; pathogen; public health relevance; receptor; response; tissue repair; tool

DESCRIPTION (provided by applicant): HIV-associated immune suppression contributes to increased colonization of commensal and opportunistic pathogens in the mouth, leading to oral complications in many HIV-infected patients. With the increasing number of HIV cases and longer life-expectancy of HIV patients, HIV-associated periodontal disease is expanding as a major health care issue. We hypothesize that HIV infection of tissue resident macrophages contribute directly to this compromise in oralpharyngeal immunity and enhanced host sensitivity to periodontal pathogens, such as the anaerobic bacterium Porphyromonas gingivalis. We are proposing to employ tissue resident macrophages from the oral cavity, specifically palatine tonsils, as a tractable primary cell model to study how HIV impacts macrophage function and associated oral pathogenesis. In addition, we propose determining signals that lead to epigenetic regulation in the context of the primary macrophages. An important aspect of this proposal is our ability to access clinical samples from patients with HIV and our previous experience in providing them with dental care. Using this cohort and our collective expertise, we will perform studies that complement our in vitro studies by characterizing macrophages and cytokines that are present in the oral cavities of HIV infected and control individuals. Upon completion of these studies, we expect to have novel insights into how PD infections contribute to a microenvironment that facilitates HIV replication, inflammation and further periodontal tissue destruction, directly contributing to HIV-associated oral pathogenesis.

描述(由申请人提供)：艾滋病毒相关免疫抑制有助于增加共生和机会性病原体在口腔中的定植，导致许多艾滋病毒感染患者的口腔并发症。随着HIV病例数量的增加和HIV患者预期寿命的延长，HIV相关的牙周病正在扩大为一个主要的卫生保健问题。我们推测，HIV感染组织中的巨噬细胞直接导致了口咽免疫的这种损害，并增强了宿主对牙周病原体的敏感性，如厌氧细菌牙龈卟啉单胞菌。我们建议使用口腔组织中的驻留巨噬细胞，特别是腭扁桃体，作为一个易于处理的原代细胞模型来研究HIV如何影响巨噬细胞功能和相关的口腔发病机制。此外，我们建议在初级巨噬细胞的背景下确定导致表观遗传调控的信号。这项提议的一个重要方面是我们能够获取艾滋病毒患者的临床样本，以及我们以前为他们提供牙科护理的经验。利用这一队列和我们的集体专业知识，我们将进行补充我们的体外研究的研究，方法是确定艾滋病毒感染者和对照组口腔中存在的巨噬细胞和细胞因子的特征。在这些研究完成后，我们希望对PD感染如何促进HIV复制、炎症和进一步牙周组织的微环境有新的见解 破坏，直接导致与艾滋病毒相关的口腔发病。