Innate Cellular Elements and Enteric Bacterial Infection

描述（由申请方提供）：在过去几年中，在了解T细胞免疫应答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，CD 4和CD 8 T细胞对于抵抗S感染的保护性免疫应答是必不可少的。鼠伤寒沙门氏菌，这些研究导致识别的肽表位识别的细菌特异性效应T细胞。我们还鉴定了表达IFIL的TCR γ δ作为口腔感染后的新应答群体。在这项提案中，我们计划扩大我们的研究，包括调查先天免疫系统（NK和NKT细胞）的细胞成分在控制沙门氏菌感染进展中的作用。我们将集中努力实现以下目标： 目标1。NK细胞是否在限制S.口腔感染后的鼠伤寒沙门氏菌？NK细胞是否影响早期先天性免疫应答或后期适应性T细胞介导的对沙门氏菌的免疫应答。鼠伤寒？ 目标二。NKT细胞在限制细菌感染中发挥作用吗？这是否会影响细菌清除和/或先天性和/或适应性免疫反应的发展？ 本提案中包含的研究旨在说明先天性淋巴样成分在清除感染和产生对革兰氏阴性病原体鼠伤寒沙门氏菌模型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，这些策略将引起有效的保护性免疫，并有助于理解革兰氏阴性病原体感染与自身免疫性疾病发展之间的病因学联系。鉴于小鼠模型中的许多细胞受体具有人类对应物，我们认为这种小鼠模型将产生有价值的信息，可应用于人类环境。

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.