Immune Evasion Mechanisms in Lyme Disease

莱姆病的免疫逃避机制

• 批准号: 6661300
• 负责人: RICHARD T MARCONI
• 金额: $ 36.37万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661300
• 关键词: Borrelia; Lyme disease; SCID mouse; active immunization; antibacterial antibody; bacteria infection mechanism; bacterial cytopathogenic effect; bacterial proteins; bactericidal immunity; gene deletion mutation; gene environment interaction; gene expression; genotype; homeobox genes; host organism interaction; humoral immunity; immunogenetics; immunoglobulin G; immunoglobulin M; laboratory mouse; polymerase chain reaction; protein structure function; ticks

DESCRIPTION (provided by applicant): Lyme Disease (LD) continues to be a serious health problem in the USA. The chronic nature of the infection can lead to debilitating and serious clinical manifestations. While early diagnosis of LD is the key to successful treatment, accurate diagnosis continues to be a significant problem. In addition, while a vaccine has been developed and licensed there are concerns about the duration of protection it affords and about possible autoimmune responses (IR) in certain genetic backgrounds. These concerns highlight the need for a better understanding of the genetic and antigenic properties of this organism and the molecular mechanisms associated with chronic infection. Our studies on chronic infection and immune evasion by B. burgdorferi (Bb) have focused on a diverse group of plasmid-carried genes and operons that are 5'-flanked by a common upstream promoter-carrying sequence that we call the upstream homology box or UHB element. UHB-flanked genes are organized into 3 distinct gene families: the ospE family, the ospF family, and family 163 (a TIGR designation). The data described below demonstrate that the ospE gene family undergoes mutational and recombinational changes during infection. In addition, members of the ospF gene family are temporally expressed during infection. These different processes culminate in the presentation of new antigenic variants of OspE and OspF on the cell surface that can contribute to immune evasion. Little is known about the role of other UHB-flanked gene families in chronic infection and immune evasion. However, the polymorphic nature of these genes suggests that their organization has been influenced by recent molecular events that may include recombination and rearrangement. The major hypotheses of this proposal are that the OspE, OspF and family 163 proteins contribute to immune evasion in LD and play stage specific roles during infection. The analyses described within will also test the utility of these proteins in vaccine development.

描述（由申请人提供）：莱姆病（LD）在美国仍然是一个严重的健康问题。感染的慢性性质会导致衰弱和严重的临床表现。尽管LD的早期诊断是成功治疗的关键，但准确的诊断仍然是一个重大问题。此外，虽然已经开发了疫苗并获得了许可，但人们担心它提供的保护持续时间以及在某些遗传背景下可能的自身免疫反应（IR）。这些关注的是，需要更好地了解该生物的遗传和抗原特性以及与慢性感染相关的分子机制。我们对B.b。brgdorferi（BB）对慢性感染和免疫逃避的研究的研究重点是一组多样化的质粒基因和操纵子，这些基因和操纵子是5'FANK，由共同的上游启动子携带者携带的序列，我们称之为上游同源性盒或UHB元素。 UHB浮装基因被组织成3个不同的基因家族：OSPE家族，OSPF家族和163家族（TIGR指定）。下面描述的数据表明，OSPE基因家族在感染过程中经历了突变和重组变化。此外，OSPF基因家族的成员在感染期间暂时表达。这些不同的过程在细胞表面上的新型OSPE和OSPF的新抗原变异剂的表达中达到顶峰，这可能有助于免疫逃避。关于其他UHB频畅基因家族在慢性感染和免疫逃避中的作用知之甚少。但是，这些基因的多态性性质表明，它们的组织受到最近可能包括重组和重排的分子事件的影响。该提案的主要假设是OSPE，OSPF和家族163蛋白在感染过程中有助于LD的免疫逃避和发挥特定的作用。其中描述的分析还将测试这些蛋白质在疫苗开发中的效用。