INFLAMMATION IN RESISTANCE TO BACTERIAL INFECTION

抵抗细菌感染的炎症

• 批准号: 3131352
• 负责人: CHARLES Joseph CZUPRYNSKI
• 金额: $ 13.02万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3131352
• 关键词: Listeria; Listeria infections; cellular immunity; cytolysis; cytotoxic T lymphocyte; helper T lymphocyte; host organism interaction; immunocytochemistry; in situ hybridization; inflammation; interferons; interleukin 1; interleukin 2; interleukin 4; interleukin 5; laboratory mouse; macrophage; monoclonal antibody; northern blottings; passive immunization; spleen; tumor necrosis factor alpha

Facultative intracellular pathogens continue to pose an important threat to human health, particularly in those whose resistance is impaired by some underlying immunodeficiency. Formerly it was thought that protective immunity against this group of pathogens depended chiefly on T helper cell activation of macrophage bactericidal activity. More recently, it has become evident that there are additional cellular and molecular interactions that substantially influence the pathogenesis of these infections. Murine listeriosis has provided a valuable model for investigating host defense mechanisms to facultative intracellular pathogens. Previous work from our laboratory has demonstrated that several soluble mediators (cytokines) are capable of substantially augmenting host defense. In addition, studies in this and other laboratories have differentiated the contributions of T cell subpopulations to host defense. There are two overall objectives of the research proposed in this application. The first is to understand the integration of cytokines and T cell subsets in cellular immunity against bacterial infection. This will be addressed by in vivo experiments that will use immunocytochemistry to identify T cell subpopulations infiltrating foci of infection, and immunocytochemistry and in situ hybridization to elucidate the profile of cytokines produced by these cells at various times during the course of the infection. This information will be correlated with bacteriological and pathological evaluations of the progression of the protective host response. The second overall objective will be to study in detail the cytolytic activity of spleen cells, obtained from listeria-immunized mice, for listeria-infected macrophages in vitro. The nature of the cytolytic cells, and the mediators required for the afferent and efferent aims of the cytolytic response will be determined. Experiments will also be performed to evaluate the contributions of cytolytic cells to host defense in vivo. Besides being of value as a general model for the immunoregulation of resistance to facultative intracellular pathogens, the information obtained will also increase our understanding of the pathogenesis of listeriosis, which has emerged as a significant public health threat.

兼性胞内病原体继续构成重要威胁 对人类健康的影响，特别是对那些抵抗力受到一些 潜在的免疫缺陷以前人们认为保护性 对这组病原体免疫主要依赖于T辅助细胞 激活巨噬细胞杀菌活性。最近， 很明显，还有额外的细胞和分子 相互作用，实质上影响这些发病机制， 感染.小鼠的寄生虫病提供了一个有价值的模型， 研究宿主对兼性细胞内 病原体我们实验室以前的工作表明， 可溶性介质（细胞因子）能够显著增强宿主 防御此外，本实验室和其他实验室的研究 区分了T细胞亚群对宿主防御的贡献。 本研究提出了两个总体目标 应用程序.首先是了解细胞因子的整合， T细胞亚群与细菌感染的细胞免疫。这将 通过使用免疫细胞化学的体内实验来解决， 鉴定浸润感染病灶的T细胞亚群，和 免疫细胞化学和原位杂交来阐明 这些细胞在免疫过程中的不同时间产生的细胞因子， 感染这些信息将与细菌学和 保护性宿主进展的病理学评价 反应第二个总体目标是详细研究 脾细胞的细胞溶解活性，所述脾细胞得自经阿托伐他汀免疫的小鼠， 感染巨噬细胞的实验。细胞溶解的性质 细胞，和介质所需的传入和传出的目的， 将测定细胞溶解反应。还将进行实验 以评估溶细胞细胞对体内宿主防御的贡献。 除了作为免疫调节的一般模型有价值之外， 对兼性胞内病原体的抗性，所获得的信息 也将增加我们对阿尔茨海默病发病机制的了解， 这已经成为一个重大的公共卫生威胁。