Define the effects and mechanism of THC and CBD on IFN-I mediated inflammation and immune dysfunction during HIV infection

明确THC和CBD对HIV感染期间IFN-I介导的炎症和免疫功能障碍的影响和机制

基本信息

批准号：
10267753
负责人：
SCOTT G KITCHEN
金额：
$ 37.05万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10267753
关键词：
Affect Agonist Analgesics Animals Anti-Inflammatory Agents Antigen-Presenting Cells Antiinflammatory Effect Antiviral Agents Antiviral Response Automobile Driving Binding Biological CNR1 gene CNR2 gene Cannabidiol Cannabinoids Cannabis Cannabis sativa plant Cardiovascular Diseases Cells Chronic Clinical Management Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Complex Conflict (Psychology)Dendritic Cells Disease Disease Progression Drug usage Frequencies Functional disorder Gene Expression Genes HIV HIV Infections HIV-1 HIV-associated neurocognitive disorder Human Immune Immune System Diseases Immune system Immunocompetence In Vitro Individual Infection Inflammation Inflammatory Interferon Type I Interferon-alpha Interferons Knock-out Macaca mulatta Malignant Neoplasms Mediating Microglia Neuraxis Neurodegenerative Disorders Pathogenesis Patients Plasma Play Predisposition Property Reporting Role SIV Signal Pathway Signal Transduction Specimen T cell response T-Lymphocyte Tetrahydrocannabinol United States Viral Viral Load result Virus Replication antiretroviral therapy cannabinoid receptor cell type chronic inflammatory disease comorbidity cytokine dosage endogenous cannabinoid system exhaustion high dimensionality humanized mouse immune activation immune function immunoregulation improved in vivo knock-down latent HIV reservoir macrophage marijuana use monocyte mouse model prevent receptor response small hairpin RNA

项目摘要

Project Summary One of the hallmarks of HIV infection is chronic immune activation/inflammation, which is strongly associated with and predictive of HIV disease progression, even in patients that were successfully treated with anti-retroviral therapy (ART). We and other have shown that chronic elevation of type I IFN signaling in HIV+ individuals is a major driver in immune activation. Alleviating chronic activation may reduce disease progression and prevent or slow down progression of HIV-associated diseases, including HIV-associated neurocognitive disorders (HAND), which is fueled by inflammation in the central nervous system (CNS). In recent years, studies have suggested that major components of cannabis, namely THC and CBD, may have anti-inflammatory properties. However, the individual and combined effects and mechanisms of THC and CBD on immune activation during HIV infection remain elusive. In this project, we aim to study the individual and combined effects of THC and CBD on immune cell activation and CNS inflammation during HIV infection. We hypothesize that THC and CBD regulate IFN-I mediated inflammation differently by binding to and signaling through diverse cannabinoid receptors. We will carefully evaluate if treatment of THC and CBD have the potential to reduce chronic inflammation and improve immune function against HIV infection.

项目概要 HIV 感染的标志之一是慢性免疫激活/炎症，这与与并预测 HIV 疾病进展，即使是在接受抗逆转录病毒治疗成功的患者中治疗（ART）。我们和其他人已经证明，HIV+ 个体中 I 型干扰素信号传导的长期升高是一个免疫激活的主要驱动力。减轻慢性激活可能会减少疾病进展并预防或减缓 HIV 相关疾病的进展，包括 HIV 相关神经认知障碍 (HAND)，这是由中枢神经系统（CNS）炎症加剧的。近年来，研究表明大麻的主要成分，即 THC 和 CBD，可能具有抗炎特性。然而， THC 和 CBD 对 HIV 感染期间免疫激活的单独和联合作用和机制仍然难以捉摸。在这个项目中，我们的目标是研究 THC 和 CBD 对免疫的单独和联合影响 HIV感染期间的细胞激活和中枢神经系统炎症。我们假设 THC 和 CBD 调节 IFN-I 通过与不同的大麻素受体结合并通过其发出信号，以不同的方式介导炎症。我们将仔细评估 THC 和 CBD 的治疗是否有可能减少慢性炎症并改善抵抗艾滋病毒感染的免疫功能。