INFLAMMATION IN RESISTANCE TO BACTERIAL INFECTION

抵抗细菌感染的炎症

• 批准号: 3131355
• 负责人: CHARLES Joseph CZUPRYNSKI
• 金额: $ 7.97万
• 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 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3131355
• 关键词: Listeria infections; T lymphocyte; bactericidal immunity; cell type; cellular immunity; complement; dairy products; disease /disorder model; food chain contamination; gene expression; inflammation; laboratory mouse; macrophage; microorganism genetics; monoclonal antibody; neutrophil; passive immunization; phagocytes; spleen transplantation

Infections caused by facultative intracellular pathogens continue to be a significant health problem in the United States and througout the world. Immunotherapeutic strategies for combatting these infections would therefore be of considerable benefit. Murine listeriosis has proven to be a convenient, reproducible, and extremely informative laboratory model for studying immuno-regulation of resistance to infection by facultative intracellular pathogens. Considerable evidence has been provided by our laboratory and others linking anti-listeria resistance with the host's ability to rapidly mobilize an adequate inflammatory response against the invading bacteria. The dual role of T lymphocytes in the regulation of inflammatory responsiveness and antibacterial resistance has been indicated by adpotive transfer studies of listeria-immune T cells which showed that L3T4+ T cells mediate accumulation of inflammatory cells in vivo and Lyt2+ T cells are required for expression of antibacterial resistance. Although these studies have been quite informative, they fail to demonstrate the cellular interactions that occur in vivo when an individual first encounters an invading facultative intracellular pathogen. In the proposed study we will manipulate mouse T cell subsets in vivo by administration of monoclonal anti- L3T4 and anit Lyt2 antibodies and then determine the effect of these treatments on inflammatory responsiveness and antibacterial resistance. Soluble factors produced by these T cells will be assessed for their pro-inflammatory effects in vivo and for their influence on macrophage antibacterial activity in vitro. The possible cytotoxic actio of listeria-immune Lyt2+ T cells against literia-infected macrophages will be investigated as a potential mechanism explaining the protection mediated by these cells in vivo. Besides providing information that will further illuminate our general understanding of T cell-mediated resistance to facultative pathogens, the resuslts of this project will also be germane to the pathogenesis of human listeriosis, which has rapidly emerged as a significant public health problem due to ingestion of listeria-contaminated dairy products.

由兼性细胞内病原体引起的感染继续存在 在美国是一个严重的健康问题， 离开这个世界。 免疫策略 因此，与这些感染作斗争将具有相当大的意义。 效益 小鼠骨髓增生已被证明是一种方便， 可重复的，非常翔实的实验室模型， 研究免疫调节对感染的抵抗力， 兼性细胞内病原体。 相当多的证据已 由我们的实验室和其他人提供， 抵抗与宿主的能力，迅速动员足够的 对入侵细菌的炎症反应。 双 T淋巴细胞在炎症调节中的作用 反应性和抗菌耐药性已被表明 免疫T细胞的适应性转移研究表明， L3 T4 + T细胞介导炎性细胞的积聚， 体内和Lyt 2 + T细胞是表达抗菌素所必需的。 阻力 虽然这些研究提供了相当多的信息， 它们无法证明细胞间的相互作用， 当个体第一次遇到入侵的兼性 胞内病原体 在拟议的研究中，我们将操纵 小鼠体内T细胞亚群的单克隆抗- L3 T4和抗Lyt 2抗体，然后确定 这些治疗对炎症反应的影响， 抗菌抗性 这些T细胞产生的可溶性因子 将评估细胞的体内促炎作用 以及它们对巨噬细胞抗菌活性的影响 体外 大肠杆菌免疫Lyt 2 + T细胞的细胞毒作用 将研究细胞对抗感染了大肠杆菌的巨噬细胞， 一种潜在的机制，解释了 这些细胞在体内。 除了提供信息， 进一步阐明了我们对T细胞介导的 对兼性病原体的抗性，该项目的恢复 也将与人类乳腺癌的发病机制密切相关， 这已经迅速成为一个重大的公共卫生问题 是因为摄入了受沙门氏菌污染的乳制品