Lipoprotein expresion and adaptation of B. burgdorferi

描述（由申请方提供）：伯氏疏螺旋体引起持续的哺乳动物感染，尽管对病原体产生了强烈的免疫应答。为了避免免疫清除，B. burgdorferi必须进化出免疫逃避策略。一种充分表征的策略是VISE抗原变异。他们假设了B. Burgdorferi潜在地用于逃避免疫清除：（1）下调表面暴露的和抗体靶向的脂蛋白，和（2）获得宿主成分并保护自身。他们在解决第一个假设方面取得了进展。通过对小鼠感染过程中137个假定脂蛋白基因表达的分析，他们确定了B的两步分子适应过程。burgdorferi。对于第一步，无论初始接种的B。当伯氏螺旋体表达137个脂蛋白基因中的全部或少于40个时，螺旋体被调节以在感染后10天内转录116个基因。在第二步，即感染后17至30天，免疫选择压力迫使B。burgdorferi下调了大多数，但表达了116个基因中的33个。这种适应过程可能是B的关键步骤。如果螺旋体不能进行这个过程，病原体会在感染的早期被清除。免疫选择压力包括体液免疫和细胞免疫。在这个项目中，他们将剖析这两种反应对B的影响。使用B细胞缺陷型小鼠和T细胞缺陷型小鼠的burgdorferi适应。为了充分探索这一假设，他们还将研究免疫选择压力对B的影响。蜱载体中的burgdorferi适应，以及针对单个脂蛋白的特异性抗体对鼠宿主中基因表达的影响。 虽然大多数B。由于Burgdorferi脂蛋白基因下调，所有已知的配体结合脂蛋白在慢性感染期间持续表达，包括核心蛋白聚糖结合蛋白A和B、纤连蛋白结合蛋白和Erp蛋白。这是第二个假设的基础，即B。Bufgdorfer获得宿主成分并保护自己免受免疫清除。在这个项目中，他们还将使用核心蛋白聚糖缺陷小鼠来检验这一假设。

DESCRIPTION (provided by applicant): Borrelia burgdorferi causes persistent mammalian infection despite the development of strong immune responses to the pathogen. To avoid immune clearance, B. burgdorferi must evolve immune evasion strategies. One well-characterized strategy is VIsE antigenic variation. They have hypothesized two additional mechanisms that B. burgdorferi potentially uses to escape immune clearance: (1) to down regulate surface-exposed and antibody-targeted lipoproteins, and (2) to gain host components and protect itself. They have made progress toward addressing the first hypothesis. Through an analysis of expression of 137 putative lipoprotein genes on the course of murine infection, they have identified a two-step molecular adaptation process by B. burgdorferi. For the first step, regardless whether the initial inocula of B. burgdorferi express either all of or less than 40 of the 137 lipoprotein genes, the spirochetes are modulated to transcribe 116 of the genes within 10 days post-infection. During the second step, which occurs between 17 and 30 days post-infection, immune selection pressure forces B. burgdorferi to down-regulate most have, but expresses 33 of the 116 genes. This adaptation process could be a critical step for B. burgdorferi to proceed to chronic infection since the pathogen would be cleared at the early stage of infection if the spirochete failed to undergo the process. Immune selection pressure consists of humoral and cellular immune responses. In this project, they will dissect the influence of both responses on B. burgdorferi adaptation using B-cell-deficient mice and T-cell-deficient mice. To fully explore the hypothesis, they will also examine the influence of immune selection pressure on B. burgdorferi adaptation in the tick vector, and the influence of specific antibodies to individual lipoproteins on gene expression in the murine host. Although most of B. burgdorferi lipoprotein genes are down regulated, all known ligand-binding lipoproteins are persistently expressed during chronic infection, including decorin-binding proteins A and B, fibronectin-binding protein, and Erp proteins. This is the basis for the second hypothesis that B. bufgdorfer gains host components and protects itself from immune clearance. In this project, they will also examine this hypothesis using decorin-deficient mice.