Microfluidic Assays for Probing Neutrophil-Borrelia Interactions in Blood during Acute Lyme Disease

用于探测急性莱姆病期间血液中中性粒细胞与疏螺旋体相互作用的微流控分析

• 批准号: 10379279
• 负责人: Daniel Irimia
• 金额: $ 21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379279
• 关键词: Acute; Affect; Aftercare; American; Antibodies; Automobile Driving; Biological Assay; Blood; Blood Cells; Blood donor; Blood specimen; Borrelia; Borrelia burgdorferi; Cell Separation; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Complement; Complement Activation; Development; Diagnosis; Diagnostic; Disease; Event; Flow Cytometry; Geographic Distribution; Geography; Health; Hour; Human Pathology; Immune; Immune response; Infection; Innate Immune Response; Knowledge; Lead; Leptospira; Leptospirosis; Leukocytes; Liver Failure; Lyme Disease; Measures; Meningitis; Microbe; Microfluidic Microchips; Microfluidics; Molecular; Monitor; Morphologic artifacts; Neutrophil Activation; Order Spirochaetales; Organ; Outcome; Pathologic Processes; Pathology; Patients; Phagocytosis; Phase; Phenotype; Prevalence; Reporting; Resolution; Respiratory distress; Rest; Role; Science; Serology test; Site; Symptoms; Syphilis; Ticks; Tissues; Treponema pallidum; United States; Work; cell motility; design; diagnostic tool; experience; genomic tools; neutrophil; novel; novel diagnostics; pathogen; renal damage; response; restoration; tick bite; tool

Lyme disease (LD) is caused by infection with Borrelia burgdorferi (Bb) and represents a growing problem in the United States due to increasing prevalence and expanding geographic range. It is estimated that 300,000 cases of LD occurred in the United States in 2017. The disease course is highly variable and can include organ-specific and disseminated involvement with acute and chronic manifestations. A knowledge gap exists regarding the immune events during the dissemination of Bb in blood during acute LD. Our objective is to bridge this knowledge gap through the development of novel tools that measure neutrophil-Bb interactions in blood. In preliminary work, we demonstrate the feasibility of microfluidic assays for the study of host-pathogen interactions in blood. Specifically, we found (A) a neutrophil spontaneous motility phenotype after spiking as few as one hundred Bb in blood, (B) a similar phenotype in blood samples from acute LD patients, and (C) a key role for complement in the activation on neutrophils in blood during early interactions with Bb. Continuing these efforts, we will optimize the neutrophil-assay-design to (1) study the interactions between neutrophils and live, motile Bb at single-cell resolution (2) identify signature neutrophil responses to Bb, and (3) probe the relay function of neutrophils during complement activation in blood by small numbers of Bb. We will begin applying the new tools to measuring neutrophil functions in patients during acute LD before specific antibodies are produced, and during treatment, to evaluate the Bb clearance from blood. Overall, our study will design new tools for the diagnostic and monitoring of LD and will expand our knowledge of host responses to LD.

莱姆病（LD）是由伯氏疏螺旋体（Bb）感染引起的，并且代表了一个日益严重的问题， 在美国，由于流行率的增加和地理范围的扩大。据估计， 2017年，美国发生了LD病例。病程变化很大，可能包括 器官特异性和弥散性受累，伴有急性和慢性表现。存在知识差距 关于急性LD期间血液中Bb传播期间的免疫事件。我们的目标是 通过开发新的工具来测量Escherichi-Bb相互作用， 血在初步工作中，我们证明了微流控分析用于宿主-病原体研究的可行性 血液中的相互作用具体地，我们发现（A）在尖峰之后中性粒细胞自发运动表型为 血液中只有100个B B b，（B）急性LD患者血液样品中的相似表型，和（C）a 在与Bb的早期相互作用期间，补体在血液中中性粒细胞活化中的关键作用。继续 通过这些努力，我们将优化嗜中性粒细胞测定设计，以（1）研究中性粒细胞和 在单细胞分辨率下的活的、能动的Bb（2）识别对Bb的签名中性粒细胞应答，以及（3）探测中继 中性粒细胞在少量Bb激活血液中补体过程中的功能。我们将开始申请 在特异性抗体之前测量急性LD患者中性粒细胞功能的新工具是 在治疗过程中产生的，以评估从血液中清除Bb。总的来说，我们的研究将设计新的 工具的诊断和监测LD，并将扩大我们的知识，主机响应LD。