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。感染的慢性性质可导致衰弱和严重的临床表现。虽然 LD 的早期诊断是成功治疗的关键，但准确诊断仍然是一个重大问题。此外，虽然疫苗已经开发出来并获得许可，但人们仍然担心它提供的保护持续时间以及在某些遗传背景下可能出现的自身免疫反应（IR）。这些担忧凸显了需要更好地了解这种生物体的遗传和抗原特性以及与慢性感染相关的分子机制。我们对伯氏疏螺旋体 (Bb) 慢性感染和免疫逃避的研究主要集中在一组不同的质粒携带基因和操纵子上，这些基因和操纵子的 5' 侧翼是一个共同的上游启动子携带序列，我们称之为上游同源盒或超宽带元素。 UHB 侧翼基因分为 3 个不同的基因家族：ospE 家族、ospF 家族和家族 163（TIGR 名称）。下面描述的数据表明 ospE 基因家族在感染过程中经历突变和重组变化。此外，ospF 基因家族的成员在感染期间暂时表达。这些不同的过程最终导致 OspE 和 OspF 新的抗原变体在细胞表面呈递，从而有助于免疫逃避。人们对其他 UHB 侧翼基因家族在慢性感染和免疫逃避中的作用知之甚少。然而，这些基因的多态性表明它们的组织受到最近分子事件的影响，其中可能包括重组和重排。该提议的主要假设是 OspE、OspF 和家族 163 蛋白有助于 LD 中的免疫逃避，并在感染过程中发挥阶段特定的作用。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。