Innate Cellular Elements and Enteric Bacterial Infection

先天细胞元件和肠道细菌感染

• 批准号: 7140557
• 负责人: Mark J Soloski
• 金额: $ 23.95万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140557
• 关键词: Salmonella typhimurium; T lymphocyte; antigen presenting cell; bacteria infection mechanism; enteric bacteria; gene targeting; genetically modified animals; gram negative bacteria; host organism interaction; immune response; immunity; laboratory mouse; lymphocyte; microorganism immunology; natural killer cells

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.

描述（由申请人提供）：在过去的几年中，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（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 细胞对于针对鼠伤寒沙门氏菌感染的保护性免疫反应至关重要，并且这些研究导致了细菌特异性效应 T 细胞识别的肽表位的鉴定。此外，我们还发现表达 iffil 的 TCRgammadelta 是口腔感染后的新反应群体。在本提案中，我们计划扩大研究范围，调查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。我们将重点努力实现以下目标： 目标 1. NK 细胞是否在口腔感染后限制鼠伤寒沙门氏菌生长和/或加速其清除方面发挥作用？ NK 细胞是否会影响针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？ 目标 2. NKT 细胞在限制细菌感染方面发挥作用吗？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？ 该提案中包含的研究旨在解决先天淋巴元件在清除感染和产生针对模型革兰氏阴性病原体鼠伤寒沙门氏菌的保护性免疫中的贡献。我们希望将这一信息应用于免疫调节策略的设计，这些策略将激发有效的保护性免疫，并有助于了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都有人类对应物，我们认为该小鼠模型将产生可应用于人类环境的有价值的信息。