Host Cell Recognition of Salmonella Typhimurium

鼠伤寒沙门氏菌的宿主细胞识别

• 批准号: 6664789
• 负责人: THOMAS G PISTOLE
• 金额: $ 14万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6664789
• 关键词: Salmonella food poisoning; Salmonella typhimurium; bacterial toxins; bactericidal immunity; bacteriophage P22; cell adhesion; cell line; clinical research; confocal scanning microscopy; flow cytometry; fluorescence microscopy; gastrointestinal epithelium; genetic transduction; host organism interaction; human subject; laboratory rabbit; lipopolysaccharides; macrophage; membrane proteins; molecular shape; neutrophil; pore forming protein; protein binding; protein purification; virus antigen; virus envelope

DESCRIPTION (provided by applicant): Salmonellosis continues to be a major infectious disease in both the United States and elsewhere. The overall goal of this project is to gain a better understanding of the early events that occur during Salmonella infections. The proposed studies focus on the initial interactions of salmonellae with host defense cells, specifically neutrophils and macrophages. The first objective is to determine whether structures found on the outer surface of Salmonella, known as porins, are involved in the recognition of this pathogen by human neutrophils. Porin-deficient mutants will be compared with their corresponding wildtype counterparts in their ability to adhere to and be internalized and killed by these neutrophils. Microbial attachment will be measured using flow cytometry and fluorescence microscopy and internalization and killing, by viability assays. The second objective is to determine whether neutrophils that have passed across a model intestinal epithelial cell layer are modified in their ability to recognize and to kill Salmonella. A model has been developed in which Salmonella initiate a series of events in the intestine that result in the migration of neutrophils into the lumen. The goal of this study is to determine whether these neutrophils exhibit an enhanced ability to detect and kill these bacterial pathogens. The third objective focuses on the ability of purified porins to block the attachment of Salmonella to host defense cells. Highly purified porins and porin-lipopolysaccharide complexes will be used in in vitro competition studies. Taken together, these studies are expected to provide a better understanding of the early cellular events in Salmonella infections.

描述（由申请人提供）：沙门氏菌病仍然是美国和其他地方的主要传染病。 该项目的总体目标是更好地了解沙门氏菌感染期间发生的早期事件。 拟议的研究重点是沙门氏菌与宿主防御细胞（特别是中性粒细胞和巨噬细胞）的初始相互作用。 第一个目标是确定沙门氏菌外表面发现的结构（称为孔蛋白）是否参与人类中性粒细胞对该病原体的识别。 将孔蛋白缺陷突变体与相应的野生型突变体粘附并被这些中性粒细胞内化和杀死的能力进行比较。 将使用流式细胞术和荧光显微镜测量微生物附着，并通过活力测定来测量内化和杀灭。 第二个目标是确定穿过模型肠上皮细胞层的中性粒细胞识别和杀死沙门氏菌的能力是否发生改变。 已经开发出一种模型，其中沙门氏菌在肠道中引发一系列事件，导致中性粒细胞迁移到管腔中。 这项研究的目的是确定这些中性粒细胞是否表现出增强的检测和杀死这些细菌病原体的能力。 第三个目标集中于纯化的孔蛋白阻止沙门氏菌附着于宿主防御细胞的能力。 高度纯化的孔蛋白和孔蛋白-脂多糖复合物将用于体外竞争研究。 总而言之，这些研究有望更好地了解沙门氏菌感染的早期细胞事件。