Virulence Mechanisms of Salmonella Typhi

伤寒沙门氏菌的毒力机制

• 批准号: 6954272
• 负责人: Andreas J Baumler
• 金额: $ 18.94万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954272
• 关键词: Salmonella typhi; antigen antibody reaction; bacteria infection mechanism; bacterial antigens; bacterial capsules; bacterial genetics; cell line; gene expression; host organism interaction; immunity; phagocytosis; receptor binding; toll like receptor; transfection; typhoids; vesicle /vacuole; virulence

DESCRIPTION (provided by applicant): Salmonella enterica serotype Typhi causes a severe systemic infection in humans, termed typhoid fever, which is responsible for some 600,000 deaths annually. Our long-range goal is to elucidate the molecular mechanisms involved in the pathogenesis of typhoid fever. The objectives of this application are to study the mechanism by which a S. Typhi-specific virulence factor, the Vi capsular antigen, contributes to host pathogen interaction. Our central hypothesis is that expression of the Vi-antigen blocks innate immune recognition of a subset of pathogen associated molecular patterns (PAMPs), thereby altering interaction with host cells. We will test different aspects of our hypothesis and accomplish the objectives of this application by pursuing the following two specific aims. 1. Determine whether expression of the Vi capsular antigen can block Toll-like receptor (TLR) recognition of known S. Typhi PAMPs. 2. Determine whether expression of the Vi antigen affects phagocytosis, phagosome maturation and survival of S. Typhi in human macrophages. The proposed work is innovative because it challenges the dogma that expression of a polysaccharide capsule serves mainly to avoid phagocytosis. It is our expectation that our approach will establish the role of the Vi antigen in evasion of TLR recognition during typhoid fever. This outcome will be significant because it promises to establish a new paradigm in host pathogen interaction that may be applicable to a number of other capsulated pathogens.

描述（由申请人提供）：伤寒沙门氏菌血清型会引起人类严重的全身感染，称为伤寒，每年导致约 60 万人死亡。我们的长期目标是阐明伤寒发病机制的分子机制。本申请的目的是研究伤寒沙门氏菌特异性毒力因子 Vi 荚膜抗原促进宿主病原体相互作用的机制。我们的中心假设是，Vi 抗原的表达会阻断对病原体相关分子模式 (PAMP) 子集的先天免疫识别，从而改变与宿主细胞的相互作用。我们将测试我们假设的不同方面，并通过追求以下两个具体目标来实现此应用程序的目标。 1. 确定 Vi 荚膜抗原的表达是否可以阻断 Toll 样受体 (TLR) 对已知伤寒沙门氏菌 PAMP 的识别。 2.确定Vi抗原的表达是否影响人巨噬细胞中伤寒沙门氏菌的吞噬作用、吞噬体成熟和存活。这项工作具有创新性，因为它挑战了多糖胶囊的表达主要用于避免吞噬作用的教条。我们期望我们的方法能够确定 Vi 抗原在伤寒期间逃避 TLR 识别的作用。这一结果将具有重要意义，因为它有望在宿主病原体相互作用中建立一个新的范式，该范式可能适用于许多其他荚膜病原体。