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

• 批准号: 10657439
• 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
• 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/10657439
• 关键词: Acceleration; Affect; Agonist; Analgesics; Animals; Anti-Inflammatory Agents; Antigen-Presenting Cells; Antiinflammatory Effect; Antiviral Response; Automobile Driving; Binding; Biological; CNR1 gene; CNR2 gene; Cannabidiol; Cannabinoids; Cannabis; Cannabis sativa plant; Cardiovascular Diseases; Cells; Central Nervous System; Chronic; Clinical Management; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Combined Modality Therapy; Complex; 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; Macrophage; Malignant Neoplasms; Mediating; Microglia; Neurodegenerative Disorders; Pathogenesis; Patients; Persons; Plasma; Play; Predisposition; Property; Reporting; Role; SIV; Signal Pathway; Signal Transduction; Specimen; T cell response; T-Lymphocyte; THC receptor; Tetrahydrocannabinol; United States; Viral; Viral Load result; Virus Replication; antagonist; 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; marijuana use; monocyte; mouse model; prevent; receptor; response; small hairpin RNA

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.

项目摘要 HIV感染的标志之一是慢性免疫激活/炎症，这与HIV感染密切相关。 即使在成功接受抗逆转录病毒治疗的患者中， 治疗（ART）。我们和其他人已经表明，在HIV+个体中I型IFN信号的慢性升高是一种免疫抑制剂。 免疫激活的主要驱动力缓解慢性激活可以减少疾病进展并预防或 减缓艾滋病毒相关疾病的进展，包括艾滋病毒相关神经认知障碍（HAND）， 其由中枢神经系统（CNS）中的炎症提供燃料。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，在这方面， THC和CBD对HIV感染期间免疫激活的单独和联合作用及机制 仍然难以捉摸在这个项目中，我们的目标是研究THC和CBD对免疫系统的单独和联合作用。 细胞活化和CNS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不同的大麻素受体进行信号传导，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， 对HIV感染的免疫功能。