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（由申请方提供）：HIV相关的免疫抑制有助于口腔内的细菌和机会致病菌定植增加，导致许多HIV感染患者的口腔并发症。随着HIV感染病例的增加和HIV患者寿命的延长，HIV相关牙周病正在扩大成为一个主要的卫生保健问题。我们推测，HIV感染的组织驻留巨噬细胞直接有助于这种妥协口咽免疫和增强宿主对牙周病原体的敏感性，如厌氧菌牙龈卟啉单胞菌。我们建议采用组织驻留巨噬细胞从口腔，特别是腭扁桃体，作为一个易处理的原代细胞模型，研究艾滋病毒如何影响巨噬细胞的功能和相关的口腔发病机制。此外，我们建议确定信号，导致表观遗传调控的背景下，主要的巨噬细胞。这项建议的一个重要方面是我们能够获得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研究，以补充我们的体外研究。在完成这些研究后，我们希望对PD感染如何促进促进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HIV相关的口腔发病机制。