Mechanisms of Listeria-Specific Immunity

这个项目的目标是确定对单核细胞增多性李斯特菌的免疫反应是如何 受抗原提呈细胞激活的调节。李斯特菌通过一种 模式识别受体和信号适配器的网络。信号被传递到 细菌的毒力和保护性的形成需要细胞质的进入。 豁免权。同样，通过Toll样受体适配器MyD88发出的信号对于 很大一部分DC成熟反应是由李斯特菌感染引起的。我们已经确定了 许多关键分子在DC中由李斯特菌胞质进入诱导。我们决定， DC共刺激分子和炎性细胞因子的表达依赖于 溶血素、LLO的表达与细菌胞浆进入。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。我们现在就会 通过检测Toll样蛋白的作用探讨李斯特菌诱导DC成熟的分子基础 受体、TLR适配器和胞浆受体与特定目标1中建议的研究。 也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 李斯特菌感染的树突状细胞作为体内免疫原。然后我们将确定共刺激分子的作用 李斯特菌感染诱导的分子和细胞因子在免疫突触形成中的作用 这些新的研究将揭示T的相互作用是如何 感染了抗原提呈细胞的细胞会产生保护性T细胞反应。我们的研究将 为这种胞内细菌与宿主免疫的相互作用提供了重要的见解 并将有助于设计针对这种病原体的有效疫苗。

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.