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Borrelia burgdorferi（BB）感染引起的，代表了日益增长的问题 由于越来越多的流行和扩大地理范围，美国。据估计有30万 LD病例发生在2017年美国。该病程差异很大，可以包括 器官特异性和传播涉及急性和慢性表现。存在知识差距 关于急性LD期间BB传播过程中的免疫事件。我们的目标是 通过开发新的工具来弥合这种知识差距 血。在初步工作中，我们证明了微流体测定的可行性 血液中的相互作用。具体而言，我们发现（a）峰值后中性粒细胞自发运动表型 血液中的一百个BB很少，（b）来自急性LD患者的血液样本中的类似表型，（c）a 早期与BB相互作用期间，在血液中嗜中性粒细胞激活中补体的关键作用。继续 这些努力，我们将优化中性粒细胞指定设计，以研究中性粒细胞与中性粒细胞之间的相互作用 单细胞分辨率下的现场运动BB（2）识别对BB的签名中性粒细胞反应，（3）探测继电器 少量BB在血液中补体激活过程中中性粒细胞的功能。我们将开始申请 在特定抗体之前，在急性LD期间测量中性粒细胞功能的新工具是 在治疗过程中产生并评估血液中的BB清除率。总体而言，我们的研究将设计新的 诊断和监测LD的工具，并将扩展我们对宿主对LD响应的了解。