Leukotrienes in Innate and Adaptive Antiviral Immunity

先天性和适应性抗病毒免疫中的白三烯

• 批准号: 7658164
• 负责人: Christopher C Norbury
• 金额: $ 34.25万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658164
• 关键词: Address; Anabolism; Antigen Presentation; Antigen-Presenting Cells; Antigens; Antiviral Agents; Antiviral Response; Arachidonic Acids; CD8B1 gene; Cells; Cellular Infiltration; Cessation of life; Data; Dendritic Cells; Dermal; Disease; Enzymes; Epidermis; Family; Gene Targeting; Generations; Goals; Health Hazards; Human; Immune response; Immunity; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interferon Type I; Investigation; Knowledge; Langerhans cell; Leukotriene Antagonists; Leukotriene C4; Leukotrienes; Lung; Lymph; Lymphoid; Mediating; Mediator of activation protein; Molecular; Morbidity - disease rate; Mus; Organ; P-Glycoprotein; Phase; Population; Process; Production; Public Health; Research; Research Personnel; Role; Secondary to; Severities; Site; Skin; T-Cell Activation; T-Lymphocyte; Vaccination; Vaccines; Vaccinia virus; Viral Antigens; Virus; Virus Diseases; Virus Replication; Wild Type Mouse; cell motility; cell type; cysteinyl-leukotriene; design; extracellular; in vivo; insight; lipid mediator; lymph nodes; macrophage; migration; mortality; neutrophil; novel; pathogen; prevent; programs; receptor; research study; response

DESCRIPTION (provided by applicant): Viral infections cause widespread death and disease in the human population. The long-range goal of our program is to define the cellular and molecular mechanisms involved in the generation of an efficient protective antiviral immune response. An antiviral immune response is comprised of innate and adaptive components. In the absence of an effective innate antiviral response the efficacy of the subsequent adaptive response is blunted. A major component of the innate inflammatory immune response is the release of bioactive arachidonic acids metabolites mediators, including leukotrienes. Leukotrienes can mediate both the local inflammatory response that can slow virus replication, and the migration of antigen presenting cells that are vital for the initiation of a productive adaptive antiviral response. Knowledge of the processes involved in successful generation of a protective antiviral immune response is incomplete with an understanding of the role of leukotrienes in the initiation of innate and adaptive responses. To date, the role of these innate inflammatory mediators in initiation of a protective antiviral immune response is unknown. Our current objective is to examine the role leukotrienes in the initiation of both the innate and adaptive immune responses to virus infection. The hypothesis in our studies is that leukotrienes function to reduce the severity of a viral infection in the skin, in addition to their role in stimulating the exodus of antigen bearing cells that are then able to stimulate a productive antiviral T cell response. To achieve this objective, three specific aims are proposed: (I) To determine the role of cysteinyl leukotrienes in inflammation following dermal infection with vaccinia virus; (II) To determine the role of leukotrienes in plasmacytoid dendritic cell distribution and function following dermal virus infection and; (III) To determine the role of cysteinyl leukotrienes in the transport of antigen from a dermal site of virus infection to the lymph node, and subsequent T cell activation. The rationale for the proposed research is that an understanding of the role of leukotrienes in antiviral responses is critical for the rationale designs of antiviral drugs and vaccines. At the completion of this project we will expect to have identified the mechanisms by which leukotrienes mediate innate and adaptive antiviral immunity.

描述（由申请人提供）：病毒感染导致人口中广泛的死亡和疾病。我们程序的远距离目标是定义与有效保护性抗病毒免疫反应产生有关的细胞和分子机制。抗病毒免疫反应由先天和适应性成分组成。在没有有效的先天抗病毒反应的情况下，随后的自适应反应的功效被削弱了。先天炎症免疫反应的一个主要组成部分是生物活性花生四烯酸代谢物介质（包括白三烯）的释放。白细胞可以介导可以减缓病毒复制的局部炎症反应，也可以介导抗原呈现细胞的迁移，这对于启动生产性适应性抗病毒反应至关重要。了解成功生成保护性抗病毒免疫反应所涉及的过程的知识是不完整的，这是对白细胞在启动先天和适应性反应中的作用的理解。迄今为止，这些先天炎症介质在启动保护性抗病毒药免疫反应中的作用尚不清楚。我们目前的目标是检查白细胞在开始对病毒感染的先天和适应性免疫反应启动中的作用。我们的研究中的假设是，除了它们在刺激抗原轴承细胞的外流中的作用外，白细胞的作用可降低皮肤中病毒感染的严重程度，然后它们能够刺激生产性抗病毒T细胞反应。为了实现这一目标，提出了三个具体目标：（i）确定白细胞三烯在真皮病毒感染后炎症中的作用； （ii）确定白三烯在皮肤病毒感染后的浆细胞类树突状细胞分布和功能中的作用； （iii）确定白细胞三烯在抗原从病毒感染的真皮部位转移到淋巴结中的作用，以及随后的T细胞激活。拟议的研究的理由是，了解白细胞在抗病毒反应中的作用对于抗病毒药物和疫苗的基本原理设计至关重要。该项目完成时，我们将期望确定白细胞介导先天性和适应性抗病毒药的机制。