Innate Cellular Elements and Enteric Bacterial Infection

描述(由申请人提供)：在过去几年中，在了解T细胞免疫反应与清除革兰氏阴性病原体鼠伤寒沙门氏菌(一种B类病原体)的相关性方面取得了重大进展。我们和其他人已经确定，CD4和CDS T细胞对于抵抗鼠伤寒沙门氏菌感染的保护性免疫反应是必不可少的，这些研究导致了细菌特异性效应T细胞识别的多肽表位的识别。此外，我们还发现TCRGammadelta在口腔感染后表达iFIL是一种新的反应人群。在这项提案中，我们计划扩大我们的研究范围，以包括对先天免疫系统的细胞成分(NK和NKT细胞)在控制沙门氏菌感染进展中的作用的调查。我们将着力抓好以下几个方面： 目的1.口腔感染后NK细胞是否在限制鼠伤寒沙门氏菌的生长和/或加速其清除方面发挥作用？NK细胞是否影响对鼠伤寒沙门氏菌的早期先天反应或后来的适应性T细胞介导的免疫反应的发展？ 目的2.NKT细胞是否在限制细菌感染方面发挥作用？这是否影响细菌清除和/或先天和/或获得性免疫反应的发展？ 这项建议中所载的研究旨在探讨先天淋巴成分在清除感染和产生对模式革兰氏阴性病原体鼠伤寒沙门氏菌的保护性免疫中的作用。我们希望将这些信息应用于免疫调节策略的设计，这些策略将激发强大的保护性免疫，并有助于理解自身免疫性疾病发展过程中感染革兰氏阴性病原体之间的病因学联系。鉴于小鼠模型中的许多细胞受体都有人类对应的受体，我们认为这个小鼠模型将产生有价值的信息，这些信息可能适用于人类环境。

DESCRIPTION (provided by applicant): In the last several years, significant progress has been made in understanding the relevance of the T cell immune response to the clearance of the Gram-negative pathogen Salmonella typhimurium, a category B pathogen. We and others, have established that both CD4 and CDS T cells are essential to the protective immune response against infection with S. typhimurium, and these studies led to the identification of peptide epitopes recognized by bacteria-specific effector T cells. Also we have identified TCRgammadelta expressing iffiLs as a novel responding population following oral infection. In this proposal we plan to expand our studies to include an investigation into the role of cellular elements of the innate immune system (NK and NKT cells) in controlling the progression of Salmonella infection. We will focus our efforts on the following Aims: Aim 1. Do NK cells play a role in limiting the growth and/or accelerating the clearance of S. typhimurium following oral infection? Do NK cells influence the development of early innate response or a later adaptive T cell-mediated immune response to S. typhimurium? Aim 2. Do NKT cells play a role in limiting bacterial infection? Does this influence bacterial clearance and/or the development of a innate and/or adaptive immune response? The studies contained in this proposal are designed to address the contribution of lymphoid elements of the innate in the clearance of infection and the generation of protective immunity to a model Gram-negative pathogen Salmonella typhimurium. We hope to apply this in formation to the design of immune-modulating strategies that will evoke potent protective immunity as well as contribute to understanding the etiological link between infection with gram-negative pathogens in the development of autoimmune disease. Given that many of the cellular receptors in the mouse model have human counterparts, we argue that this murine model will yield valuable information that may be applied to the human setting.