A microbial antigen as a molecular trigger of Lyme borreliosis

微生物抗原作为莱姆疏螺旋体病的分子触发因素

• 批准号: 8475424
• 负责人: Xiuli Yang
• 金额: $ 7.6万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8475424
• 关键词: Antigens; Arthritis; Borrelia burgdorferi; CXCL1 gene; CXCL5 gene; Cells; Chemotaxis; Clinical; Complement; Cytokine Receptors; Data; Development; Disease; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Goals; Human; IL8RB gene; Immune response; In Vitro; Infection; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Joints; Kinetics; Lipoproteins; Lyme Arthritis; Lyme Disease; Measures; Mediating; Membrane Proteins; Molecular; Mus; Neutrophil Infiltration; Order Spirochaetales; Outcome; Pathogenesis; Patients; Play; Preventive; Production; Property; Proteins; Publishing; Recruitment Activity; Reverse Transcriptase Polymerase Chain Reaction; Role; SCID Mice; Surface; Synovial Cell; Therapeutic; Tissues; Virulence; chemokine; chemokine receptor; cytokine; in vivo; insight; interest; microorganism antigen; mutant; neutrophil; pathogen; receptor

DESCRIPTION (provided by applicant): We propose to determine whether and how one of the Borrelia burgdorferi surface exposed proteins, Lmp1, functions as a molecular trigger for the induction of host inflammatory responses. Arthritis is one of the most frequent clinical complications of Lyme borreliosis, which results from the infection with the bacterial pathogen Borrelia burgdorferi. Without proper treatment, arthritis is manifested in approximately 60% of the infected patients. A severe infiltration of the inflammatory cells (mostly neutrophil) is a majr feature of Lyme arthritis that contributes to severe pathological damage in the infected joint. Previous studies have demonstrated that B. burgdorferi possesses potent cytokine-stimulating properties and that spirochete lipoproteins induce the production of pro-inflammatory cytokines. Our recent studies involving one of the B. burgdorferi gene products showed that the antigen Lmp1, also annotated as surface-located membrane protein 1, is a virulence determinant of the Lyme disease pathogen. The presence of Lmp1 assists the spirochete to evade host adaptive immune responses. Our preliminary data suggests that although Lmp1-deficient B. burgdorferi persists in severe combined immunodeficient (SCID) mice, unlike wild type spirochetes, these isogenic mutants are unable to induce severe disease. We hypothesize that Lmp1 could contribute to host inflammatory responses subsequently leading to the complications of Lyme borreliosis. The goal of this proposal is to study the potential role of Lmp1 as a molecular trigge of host inflammatory responses. This study will provide new insights into the pathogenesis of Lyme borreliosis and help developing preventive measures against Lyme arthritis.

描述（由申请人提供）：我们建议确定是否以及如何以及如何以及如何以及如何用作诱导宿主炎症反应的分子触发蛋白LMP1。关节炎是莱姆毛毛病的最常见临床并发症之一，这是由于细菌病原体伯氏伯氏菌的感染而引起的。没有适当的治疗，大约60％的感染患者表现出关节炎。炎性细胞（主要是嗜中性粒细胞）的严重浸润是莱姆关节炎的MAJR特征，导致感染关节严重的病理损害。先前的研究表明，B。burgdorferi具有有效的细胞因子刺激特性，并且螺旋体脂蛋白诱导促炎性细胞因子的产生。我们最近涉及B. burgdorferi基因产物之一的研究表明，抗原LMP1（也被注释为表面上的膜蛋白1）是莱姆病病原体的毒力决定因素。 LMP1的存在有助于螺旋体逃避宿主的适应性免疫反应。我们的初步数据表明，尽管LMP1缺陷型伯氏杆菌持续存在于严重组合的免疫缺陷（SCID）小鼠中，但与野生型螺旋体不同，这些等遗传突变体无法诱导严重的疾病。我们假设LMP1可能有助于宿主的炎症反应，从而导致莱姆毛毛病的并发症。该提案的目的是研究LMP1作为宿主炎症反应的分子触发的潜在作用。这项研究将为莱姆毛毛病的发病机理提供新的见解，并有助于制定针对莱姆关节炎的预防措施。