INFLAMMATION IN RESISTANCE TO BACTERIAL INFECTION

抵抗细菌感染的炎症

• 批准号: 3131357
• 负责人: CHARLES Joseph CZUPRYNSKI
• 金额: $ 12.7万
• 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/3131357
• 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.

兼性细胞内病原体继续构成重要威胁 对人类健康，特别是对那些抵抗力受到某些损害的人 潜在的免疫缺陷。以前，人们认为保护性的 对这组病原体的免疫主要依靠辅助性T细胞 激活巨噬细胞杀菌活性。最近，它已经 很明显，还有额外的细胞和分子 在很大程度上影响这些疾病发病机制的相互作用 感染。小鼠李斯特氏菌病提供了一个有价值的模型 寄主对兼性胞内防御机制的研究 病原体。我们实验室之前的工作已经证明了几个 可溶性介体(细胞因子)能够显著增强宿主 防守。此外，该实验室和其他实验室的研究已经 区分T细胞亚群对宿主防御的贡献。 本文提出的研究总体目标有两个 申请。首先是了解细胞因子和细胞因子的整合 T细胞亚群在抗细菌感染细胞免疫中的作用。这将是 通过体内实验解决，这些实验将使用免疫细胞化学来 确定T细胞亚群浸润性感染灶，以及 免疫细胞化学和原位杂交法研究细胞外基质的表达 这些细胞在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 回应。第二个总体目标是详细研究 从李斯特菌免疫的小鼠中获得的脾细胞的杀伤活性， 用于体外感染李斯特菌的巨噬细胞。细胞溶解的性质 细胞，以及细胞传入和传出目的所需的介体 将测定细胞溶解反应。还将进行实验 目的：评价体内溶细胞在宿主防御中的作用。 此外，作为免疫调节的通用模型，它还具有价值 对兼性细胞内病原菌的抗性，获得的信息 也将增加我们对李斯特菌病发病机制的了解， 它已经成为一个重大的公共卫生威胁。