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）：与 HIV 相关的免疫抑制会增加口腔中共生和机会性病原体的定植，从而导致许多 HIV 感染患者出现口腔并发症。随着艾滋病毒病例数量的增加和艾滋病毒患者预期寿命的延长，与艾滋病毒相关的牙周病正在成为一个主要的卫生保健问题。我们假设组织驻留巨噬细胞的 HIV 感染直接导致口咽部免疫的这种损害，并增强宿主对牙周病原体（例如厌氧细菌牙龈卟啉单胞菌）的敏感性。我们建议利用口腔中的组织驻留巨噬细胞，特别是腭扁桃体，作为易于处理的原代细胞模型，以研究艾滋病毒如何影响巨噬细胞功能和相关的口腔发病机制。此外，我们建议确定在初级巨噬细胞中导致表观遗传调控的信号。该提案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之前为他们提供牙科护理的经验。利用这个队列和我们的集体专业知识，我们将通过表征 HIV 感染者和对照个体口腔中存在的巨噬细胞和细胞因子来进行补充我们的体外研究的研究。完成这些研究后，我们期望对 PD 感染如何形成促进 HIV 复制、炎症和进一步牙周组织的微环境有新的见解 破坏，直接导致艾滋病毒相关的口腔发病机制。