Factors Affecting Dissemination Events Early in Bubonic Plague

影响黑死病早期传播事件的因素

基本信息

批准号：
8605167
负责人：
VIRGINIA L MILLER
金额：
$ 22.62万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-15 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8605167
关键词：
Aerosols Affect Antigens Appearance Arthropods Bacteria Belief Biological Assay Bioterrorism Bite Bubonic Plague Cells Cessation of life Country Data Defect Development Disease Disease Progression Emerging Communicable Diseases Event Fleas Flow Cytometry Genes Genetic Goals Human Immunosuppression In Vitro Incidence Infection Infection Control Lead Lymphatic System Mammals Modeling Monitor Mutation Nature Oligonucleotides Organism Outcome Pathogenesis Patients Phagocytes Phagocytosis Plague Population Process Recording of previous events Reporting Route Shapes Site Staging Staining method Stains Surveys Testing Therapeutic Time Tissues Type III Secretion System Pathway Vaccines Virulence Virulence Factors Yersinia pestis animal ecology base capsule cell type extracellular feeding human ecology in vivo insight lymph nodes mortality mutant pandemic disease pathogen pathogenic bacteria prophylactic public health relevance response therapeutic target trafficking

项目摘要

DESCRIPTION (provided by applicant): Yersinia pestis is the causative agent of disease in a variety of mammals, and humans can become infected when human and animal ecologies intersect. This has led to several pandemics of plague in human history, and infection with Y. pestis is currently considered by the WHO as a re-emerging infectious disease because of the increased incidence in a wide number of countries. Bubonic plague is the most common form of disease and the untreated mortality rate is estimated at 40-70%. A number of recent studies from several groups suggest that Y. pestis actively causes immunosuppression early during infection. Furthermore, recent studies have shown that very early events after inoculation are responsible for determining the outcome of infection. One of the first steps in the pathogenesis of bubonic plague is dissemination of the pathogen from the inoculation site (IS) to the draining lymph node (DLN). It has long been believed that the bacteria disseminate to the DLN by trafficking in phagocytic cells. However, there is strikingly little in vivo data demonstrating this. We hypothesize that Y. pestis actively influences these early dissemination events by interacting with key components of the host innate response. Our long-term goal is to understand the mechanism of dissemination of Y. pestis from the IS to the DLN. Using an intradermal route (the route that most closely mimics that of the flea) of inoculation and a dissemination assay we recently developed, we are able to monitor the transit of bacteria to the DLN from the IS, and subsequently to systemic tissues. Here, we will specifically test in vivo (a) the widely held belief that phagocytic cells are important for traffiking Y. pestis from the IS to the DLN, and (b) effects by the Y. pestis virulence factors known to affect interactions with phagocytic cells in vitro for their impact on early dissemination to the DLN.

描述（由申请人提供）：耶尔森氏菌是多种哺乳动物中疾病的病因，当人类和动物生态相交时，人类可能会被感染。这导致了人类历史上的几种大瘟疫大流行病，由于广泛的国家发生的发病率增加，WHO目前将WHO视为一种重新出现的传染病。泡沫瘟疫是最常见的疾病形式，未处理的死亡率估计为40-70％。来自几个小组的许多最新研究表明，柴杆菌在感染期间早期积极引起免疫抑制。此外，最近的研究表明，接种后非常早期的事件负责确定感染的结果。泡沫瘟疫发病机理的第一步之一是将病原体从接种部位（IS）传播到排水淋巴结（DLN）。长期以来，人们一直认为，细菌通过在吞噬细胞中运输将其传播到DLN。但是，体内数据很少有证明这一点。我们假设Y. Pestis通过与宿主先天反应的关键组成部分互动来积极影响这些早期传播事件。我们的长期目标是了解从IS到DLN传播Y. Pestis的机制。使用接种的接种途径（最紧密地模拟跳蚤的途径）和我们最近开发的传播测定法，我们能够监测细菌从IS到DLN的转运，然后从IS，然后是全身组织。在这里，我们将在体内特异性测试（a）广泛持有的信念，即吞噬细胞对从IS到DLN的鼠疫pestis很重要，以及（b）pestis毒力因素已知会影响与吞噬细胞相互作用的Y. pestis毒力因子的作用细胞在体外对早期传播到DLN的影响。