Understanding Human Immunological Responses to Ixodes Tick Bites

了解人类对硬蜱叮咬的免疫反应

• 批准号: 9807836
• 负责人: Linden T Hu
• 金额: $ 20.63万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-13 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9807836
• 关键词: Anaplasmosis; Animal Model; Animals; Antibiotic Therapy; Antibodies; Antigens; Arthropods; Artificial Feeding; Artificial Membranes; Babesiosis; Bacteria; Behavior; Belief; Biology; Biopsy; Biopsy Specimen; Bite; Black-legged Tick; Blood specimen; Borrelia burgdorferi; Borrelia miyamotoi; Cavia; Cells; Cellular Immunity; Characteristics; Collection; Data; Deer Tick; Development; Devices; Disease; Erythema; Evolution; Exposure to; Future; Goals; Histologic; Histology; Human; Immune; Immune response; Immune system; Immunity; Immunize; Immunology; Individual; Infection; Inflammatory; Inflammatory Response; Ixodes; Laboratories; Leucocytic infiltrate; Lyme Disease; Measures; Membrane; Mus; Organism; Patients; Peromyscus; Plasma; Play; Positioning Attribute; Predisposition; Pruritus; Reaction; Recording of previous events; Residual state; Resistance; Resistance development; Risk; Role; Salivary; Salivary Proteins; Sampling; Serum; Site; Skin; Specimen; Techniques; Testing; Tick-Borne Diseases; Tick-Borne Encephalitis; Tick-Borne Infections; Ticks; Time; Virus; Whole Blood; Xenodiagnosis; adaptive immune response; adaptive immunity; base; cell type; cytokine; design; disease transmission; experience; feeding; granulocyte; human disease; immunoreaction; inflammatory milieu; innovative technologies; pathogen; prevent; resistance mechanism; response; success; transcriptome; transcriptome sequencing; transcriptomics; transmission process; vector; vector tick

ABSTRACT Ixodes ticks are vectors of many important human diseases including but not limited to Lyme disease, babesiosis, anaplasmosis, Borrelia miyamotoi disease, and tick-borne encephalitis causing viruses. Animals fed on by ticks may develop resistance to repeated tick feedings and individual humans have shown differing levels of resistance to tick feeding. While much has been learned about responses to ticks in model animals, recent studies have shown that ticks alter their salivary content based on the host they are feeding on and that immunological responses to tick bites can vary significantly between hosts. Human responses to tick bites have not been studied systematically due to the difficulty in obtaining consistent, characterizable samples. Our laboratories are involved in a multi-year study to examine the use of ticks as a device (xenodiagnosis) for detecting the persistence of the Lyme disease causing organism, Borrelia burgdorferi, after antibiotic treatment in patients. As a result, we have a large, well characterized collection of serum, plasma, whole blood and skin biopsy samples from around tick bite sites. Here, in response to a specific RFA (PAR-18-860) to study the Immune Response to Arthropod feeding, we propose to study human cellular and adaptive immune responses to tick bites and attempt to correlate specific components of each with resistance to tick feeding. In Aim 1, we will examine skin biopsy samples from patients where ticks fed either poorly or well to determine the cytokine profile in response to the bite using RNAseq. We will also determine the histological characteristics of the cellular infiltrate around the tick bite site. Using spatial transcriptomics, we will examine the cellular transcriptome as it relates to the tick bite site and understand the contribution of different cell types to the inflammatory milieu. In Aim 2, we will determine the impact of the adaptive immune response on tick feeding. Using artificial feeding membranes, we will test serum from patients who experienced good and poor feeding as well as the effects of the evolving immune response over time and after multiple exposures to ticks. At the completion of this project, we will have established the human immune correlates of successful and unsuccessful tick feeding which will form the building blocks for designing future approaches to preventing tick borne diseases through interfering with tick feeding.

抽象的 ixodes tick是许多重要人类疾病的向量，包括但不限于莱姆病， 巴氏菌病，肿瘤病，宫林氏菌病和tick传播脑炎引起病毒。动物 在tick虫上喂食可能会产生对重复的滴答喂食的抵抗力，并且单个人类显示出不同的 tick喂食的阻力水平。尽管已经了解了对模型动物中tick的回应的知识，但 最近的研究表明，tick虫根据他们要喂养的宿主改变其唾液含量，并且 宿主之间对滴答叮咬的免疫反应可能会有很大差异。人类对滴答叮咬的反应 由于难以获得一致的，具有特征性的样本，因此未被系统地研究。我们的 实验室参与了一项多年研究，以检查tick用作设备（Xenodiagnosis）的使用 在抗生素治疗后，检测莱姆病的持续性，伯氏伯氏菌 在患者中。结果，我们的血清，血浆，全血和皮肤的收集很大 来自tick虫叮咬站点的活检样本。在这里，为了响应特定的RFA（PAR-18-860）来研究 免疫反应对节肢动物喂养，我们建议研究人类细胞和适应性免疫反应 滴答叮咬，并试图将每个组件的特定组件与tick喂食的阻力相关联。在AIM 1中，我们 将检查来自滴答滴答不佳或良好以确定细胞因子的患者的皮肤活检样品 使用RNASEQ响应咬合的轮廓。我们还将确定 细胞浸入壁虱咬合部位周围。使用空间转录组学，我们将检查细胞 转录组与tick叮咬位点有关，并了解不同的单元类型对 炎症环境。在AIM 2中，我们将确定自适应免疫反应对滴答喂养的影响。 使用人工喂养膜，我们将测试经历良好和喂养不佳的患者的血清 以及随着时间的流逝和多次接触后不断发展的免疫反应的影响。在 完成该项目的完成，我们将建立成功的人类免疫相关性和 不成功的tick喂食将构成设计未来方法以防止tick的构件 通过干扰tick喂食，传播疾病。