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

项目摘要 艾滋病毒感染的特征之一是慢性免疫激活/炎症，这与 即使在成功接受抗逆转录病毒治疗的患者中，也可以预测艾滋病毒疾病的进展 治疗(ART)。我们和其他人已经表明，HIV患者中I型干扰素信号的慢性升高是一种 免疫激活的主要驱动力。缓解慢性激活可能会减缓疾病的进展，预防或 减缓艾滋病毒相关疾病的进展，包括艾滋病毒相关性神经认知障碍(HAND)， 这是由中枢神经系统(CNS)的炎症推动的。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感染过程中免疫激活的单独和联合作用及其机制 仍然难以捉摸。在本项目中，我们旨在研究THC和CBD对免疫功能的单独和联合影响 HIV感染过程中的细胞活化和中枢神经系统炎症。我们假设THC和CBD调节干扰素-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发出信号，以不同的方式介导炎症。我们会 仔细评估THC和CBD的治疗是否有可能减少慢性炎症并改善 抗HIV感染的免疫功能。

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.