Mechanisms of Listeria-Specific Immunity

李斯特菌特异性免疫机制

基本信息

批准号：
7447978
负责人：
ELIZABETH HILTBOLD SCHWARTZ
金额：
$ 2.66万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-15 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7447978
关键词：
Address Affect Antigen-Presenting Cells Antigens Bacteria Bacterial Infections CD4 Positive T Lymphocytes CD8B1 gene Cell Maturation Cells Cytoplasm Cytotoxic T-Lymphocytes Dendritic Cells Development Goals Helper-Inducer T-Lymphocyte Hemolysin Imaging Techniques Immune Immune response Immune system Immunity Immunization In Vitro Individual Infection Inflammatory Interleukin-1 Invaded Life Listeria Listeria monocytogenes Mediating Microscopic Molecular Molecular Structure Mus Outcome Pattern Pattern recognition receptor Phagosomes Receptor Signaling Relative (related person)Role Signal Pathway Signal Transduction Signaling Molecule Structure T-Cell Activation T-Cell Development T-Cell Proliferation T-Lymphocyte Toll-like receptors Tyrosine Phosphorylation Vaccines Virulence base cohort cytokine cytosolic receptor design immunological synapse in vivo insight interleukin-18 receptor mutant neonate novel pathogen response synaptogenesis

项目摘要

The goal of this project is to determine how the immune response to Listeria monocytogenes is regulated by activation of antigen presenting cells. Listeria trigger APC activation through a network of pattern recognition receptors and signaling adapters. Signals transduced upon cytoplasmic entry are required for virulence of the bacteria and for development of protective immunity. Likewise, signaling through the Toll-like receptor adapter MyD88 is essential for a significant portion of the DC maturation response induced by listerial infection. We have identified many of the key molecules induced in DC by listerial cytoplasmic entry. We determined that the expression of costimulatory molecules and inflammatory cytokines by DC was dependent upon expression of the hemolysin, LLO and bacterial cytoplasmic entry. We have also determined the role of each of these molecules in priming CD8+ T cell proliferation and function. We will now explore the molecular basis for DC maturation induced by Listeria by examining the role of Toll-like receptors, TLR adapters, and cytosolic receptors with the studies proposed in Specific Aim 1. We will also determine the role of these molecules in generating protective immunity to Listeria using Listeria-infected DC as an immunogen in vivo. We will then determine the role of costimulatory molecules and cytokines induced by listerial infection in the formation of the immunological synapse with the studies proposed in specific aim 2. These novel studies will reveal how the interaction of T cells with infected antigen presenting cells gives rise to protective T cell responses. Our studies will provide important insights into the interaction of this intracellular bacteria with the host immune system and will aid the design of efficacious vaccines against this pathogen.

该项目的目的是确定对李斯特菌单核细胞增生李斯特菌的免疫反应如何受抗原呈现细胞的激活调节。李斯特菌通过A触发APC激活模式识别受体和信号适配器的网络。传递信号细胞质入口是细菌毒力和保护性的发展所必需的免疫。同样，通过Toll样受体适配器MyD88发出信号对于A至关重要 DC成熟反应的显着部分是由裂膜感染引起的。我们已经确定了腹膜细胞质进入在DC中诱导的许多关键分子。我们确定通过DC表达共刺激分子和炎性细胞因子的表达取决于血素，LLO和细菌细胞质进入的表达。我们还确定了这些分子中的每一个在启动CD8+ T细胞增殖和功能中的作用。我们现在会探索李斯特菌引起的DC成熟的分子基础，通过检查Toll样的作用受体，TLR衔接子和胞质受体与特定目标中提出的研究1。还将确定这些分子在使用李斯特菌产生保护性免疫中的作用李斯特菌感染DC作为体内免疫原。然后，我们将确定共刺激的作用腹膜感染诱导的分子和细胞因子形成免疫突触通过在特定目标2中提出的研究。这些新型研究将揭示t的相互作用如何具有感染抗原呈递细胞的细胞会导致保护性T细胞反应。我们的研究将提供有关该细胞内细菌与宿主免疫的相互作用的重要见解系统，将有助于设计有效的疫苗针对这种病原体。