OspC mediated evasion of the innate immune response by Borrelia burgdorferi

OspC 介导伯氏疏螺旋体逃避先天免疫反应

• 批准号: 7701093
• 负责人: Jennifer M Hughes
• 金额: $ 11.5万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7701093
• 关键词: Acute; Animal Diseases; Ankle; Antigens; Arthritis; Behavior; Biological Models; Bite; Black-legged Tick; Bladder; Blood; Borrelia burgdorferi; CCL2 gene; Cardiovascular system; Case Study; Cells; Chronic; Communicable Diseases; Confocal Microscopy; Development; Disease; Doctor of Philosophy; Dose; Ear; Emerging Communicable Diseases; Goals; Heart; Histologic; Hour; Human; IL8RB gene; Immune; Immune response; Inbred C3H Mice; Inbred Strains Mice; Incidence; Infection; Infectious Diseases Research; Inflammatory; Inflammatory Response; Investigation; Knockout Mice; Lipoproteins; Lyme Disease; Mediating; Membrane Proteins; Messenger RNA; Missouri; Morbidity - disease rate; Neurologic; Order Spirochaetales; Organism; OspC protein; Pathogenesis; Pathologist; Pathology; Phase; Principal Investigator; Regulation; Research; Research Personnel; Research Training; Residencies; Resistance; Scientist; Site; Skin; Source; Staging; Staining method; Stains; Structure; Surface; System; Tissues; Training; United States; Variant; Vector-transmitted infectious disease; Wild Type Mouse; Work; biosecurity; career; chemokine; chemokine receptor; clinical Diagnosis; cytokine; immune clearance; in vivo; interest; mouse model; mutant; pathogen; prevent; protein expression; response; skills; training project

DESCRIPTION (provided by applicant): Dr. Jennifer Hughes Hanks is a veterinary pathologist in the final stages of her residency training. She has a long-standing interest in the pathogenesis of infectious diseases, specifically emerging and foreign animal diseases. While Dr. Hughes Hanks has considerable training in the clinical diagnosis and behavior of a wide range of infectious diseases, her research training is limited. Her goal in the next four years is to develop the skills to become an independent researcher in the field of emerging infectious disease. This proposal describes a PhD training project which will take place in the Department of Pathobiology at the Univerisity of Missouri. The training will be supervised by Charles R. Brown, a well-established research scientist. The project will be focused on the pathogenesis of Borrelia burgdorferi, the causive agent of Lyme disease, in the mouse model. Since its discovery in the mid-1970s, Lyme disease has become the most common vector- borne infectious disease in the United States and is classified as an emerging infectious disease. While significant progress has been made in understanding the mechanisms of Lyme disease pathology, especially arthritis, little is known about the basic mechanisms of spirochete transmissibility and how it avoids immune clearance. Recent work in the mouse model has illustrated that surface lipoprotein antigens, specifically OspC, expressed by B. burgdorferi organisms are critical to the survival and dissemination of the spirochete in the mammalian host by evasion of the innate immune response. In this project, the cellular immune response will be quantified histologically during the early phase of in vivo infection by OspC-deficient spirochetes (Aim 1). The cytokine/chemokine alterations at the inoculation site of wild-type mice will be determined after challenge with OspC(-) B. burgdorferi mutants (Aim 2). Variations in survivability of OspC- deficient spirochetes will be examined in KC, CXCR2, MCP-1, and CCR2 cytokine knockout mice (Aim 3). At the completion of the project, Dr. Hughes will be better equipped to achieve her long-term career objective of aiding in national biosecurity efforts by helping to prevent the spread of emerging and foreign animal diseases.

描述（由申请人提供）：詹妮弗·休斯·汉克斯博士是一名兽医病理学家，正处于住院医师培训的最后阶段。她对传染病的发病机理有着长期的兴趣，特别是新兴的和外来的动物疾病。虽然Hughes Hanks博士在各种传染病的临床诊断和行为方面接受了相当多的培训，但她的研究培训有限。她在未来四年的目标是发展技能，成为新兴传染病领域的独立研究人员。本建议书描述了一个将在密苏里州大学病理生物学系进行的博士培训项目。培训将由Charles R.布朗是一位知名的研究科学家。该项目的重点是莱姆病的致病因子伯氏疏螺旋体在小鼠模型中的发病机制。莱姆病自20世纪70年代中期被发现以来，已成为美国最常见的病媒传染病，并被列为新兴传染病。虽然在理解莱姆病病理机制方面取得了重大进展，特别是关节炎，但对螺旋体传播的基本机制以及它如何避免免疫清除知之甚少。最近在小鼠模型中的研究表明，表面脂蛋白抗原，特别是OspC，由B表达。通过逃避先天免疫应答，伯氏菌生物体对于螺旋体在哺乳动物宿主中的存活和传播至关重要。在本项目中，将在OspC缺陷型螺旋体体内感染的早期阶段对细胞免疫应答进行组织学定量（目的1）。在用OspC（-）B激发后，将测定野生型小鼠接种部位的细胞因子/趋化因子变化。burgdorferi突变体（Aim 2）。将在KC、CXCR 2、MCP-1和CCR 2细胞因子敲除小鼠中检查OspC缺陷型螺旋体的存活能力的变化（Aim 3）。在该项目完成后，休斯博士将更好地实现她的长期职业目标，即通过帮助防止新出现的和外国动物疾病的传播，帮助国家生物安全工作。