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.

该项目的目标是确定对单核细胞增生李斯特氏菌的免疫反应如何受抗原呈递细胞激活的调节。李斯特菌通过a触发APC激活模式识别受体和信号适配器网络。信号转导细菌的毒力和保护性细胞的形成需要进入细胞质免疫。同样，通过 Toll 样受体适配器 MyD88 发出的信号对于由李斯特菌感染诱导的 DC 成熟反应的重要部分。我们已经确定通过李斯特菌进入细胞质在 DC 中诱导许多关键分子。我们确定 DC 共刺激分子和炎症细胞因子的表达取决于溶血素、LLO 和细菌细胞质进入的表达。我们还确定了这些分子在启动 CD8+ T 细胞增殖和功能中的作用。我们现在将通过检查 Toll-like 的作用探索李斯特菌诱导 DC 成熟的分子基础受体、TLR 接头和胞质受体以及具体目标 1 中提出的研究。我们还将确定这些分子在产生对李斯特菌的保护性免疫中的作用李斯特菌感染的 DC 作为体内免疫原。然后我们将确定共刺激的作用李斯特菌感染诱导免疫突触形成的分子和细胞因子具体目标 2 中提出的研究。这些新颖的研究将揭示 T 的相互作用如何被感染的抗原呈递细胞的细胞会产生保护性 T 细胞反应。我们的研究将为了解这种细胞内细菌与宿主免疫的相互作用提供了重要的见解系统并将有助于设计针对这种病原体的有效疫苗。