Unique impact of SIV on monocyte CNS trafficking

SIV 对单核细胞中枢神经系统运输的独特影响

• 批准号: 7252028
• 负责人: CANDICE Cynclare CLAY
• 金额: $ 1.49万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252028
• 关键词: AIDS Dementia Complex; Acquired Immunodeficiency Syndrome; Acute; Address; Bacteremia; Bacteria; Biology; Blood - brain barrier anatomy; Brain; Cells; Characteristics; Chemotactic Factors; Cytomegalovirus; Dementia; Development; Disease; Drug Delivery Systems; Encephalitis; Endothelial Cells; Equus caballus; Event; Exhibits; Exposure to; Fellowship; Fluorescein; Fluoresceins; Gastrointestinal tract structure; HIV; HIV Infections; Homing; Human; Immune; In Vitro; Individual; Infection; Infiltration; Inflammation; Lead; Leukocyte Trafficking; Listeria; Liver; Macaca; Mediating; Modeling; Names; Neuraxis; Numbers; Pathogenesis; Patients; Play; Production; Role; Route; SIV; Salmonella; Signal Transduction; Site; Spleen; Stimulus; Testing; Thinking; Time; Up-Regulation; Viral; Virus; Virus Diseases; autocrine; base; chemokine; chemokine receptor; clay; cytokine; day; extracellular; in vivo; insight; macrophage; migration; monocyte; nonhuman primate; novel; pathogen; pathogen exposure; programs; response; trafficking

DESCRIPTION (provided by applicant): Monocytes play a central role in the pathogenesis of human immunodeficiency virus (HlV)-associated dementia. They are thought to facilitate viral neuroinvasion, serving as "Trojan horse" for virus entry into the brain. However, many aspects regarding monocyte brain recruitment in HIV infection remain undefined. We hypothesize that a unique monocyte brain migratory program is triggered upon HIV infection (versus infection with other pathogens). Specific aim 1 will define in vitro monocyte migratory profiles triggered upon simian immunodeficiency virus (SIV) infection (compared to infection with CMV, Salmonella and Listeria) in response to CNS-specific chemokine signals which correlate with observed increased fluorescein+ monocyte brain infiltration in vivo. In specific aim 2, I will examine chemokine responses of SIV-infected monocytes to identify autocrine regulatory mechanisms involved in promoting continued monocyte CMS recruitment. My findings are expected to provide novel insights into mechanism(s) of monocyte neuroinvasion in the nonhuman primate model for AIDS and may lead to novel drug targeting or treatment strategies that inhibit aberrant monocyte neuroinfiltration (by targeting specific monocyte subsets or their trafficking signals).

描述（由申请人提供）：单核细胞在人类免疫缺陷病毒（HIV）相关痴呆的发病机制中起着重要作用。它们被认为是促进病毒入侵神经的“特洛伊木马”，使病毒进入大脑。然而，关于HIV感染中单核细胞脑募集的许多方面仍不明确。我们假设一个独特的单核细胞脑迁移程序是在HIV感染后触发的（与其他病原体感染相比）。具体目标1将定义在猴免疫缺陷病毒（SIV）感染（与CMV、沙门氏菌和李斯特菌感染相比）后响应CNS特异性趋化因子信号触发的体外单核细胞迁移谱，所述CNS特异性趋化因子信号与体内观察到的荧光素+单核细胞脑浸润增加相关。在具体目标2中，我将研究SIV感染单核细胞的趋化因子反应，以确定参与促进持续单核细胞CMS募集的自分泌调节机制。我的研究结果有望为非人灵长类动物模型中单核细胞神经浸润机制提供新的见解，并可能导致新的药物靶向或治疗策略，抑制异常单核细胞神经浸润（通过靶向特定的单核细胞亚群或其运输信号）。