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
基本信息
- 批准号:10379279
- 负责人:
- 金额:$ 21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AcuteAffectAftercareAmericanAntibodiesAutomobile DrivingBiological AssayBloodBlood CellsBlood donorBlood specimenBorreliaBorrelia burgdorferiCell SeparationCellsCenters for Disease Control and Prevention (U.S.)Cessation of lifeChronicComplementComplement ActivationDevelopmentDiagnosisDiagnosticDiseaseEventFlow CytometryGeographic DistributionGeographyHealthHourHuman PathologyImmuneImmune responseInfectionInnate Immune ResponseKnowledgeLeadLeptospiraLeptospirosisLeukocytesLiver FailureLyme DiseaseMeasuresMeningitisMicrobeMicrofluidic MicrochipsMicrofluidicsMolecularMonitorMorphologic artifactsNeutrophil ActivationOrder SpirochaetalesOrganOutcomePathologic ProcessesPathologyPatientsPhagocytosisPhasePhenotypePrevalenceReportingResolutionRespiratory distressRestRoleScienceSerology testSiteSymptomsSyphilisTicksTissuesTreponema pallidumUnited StatesWorkcell motilitydesigndiagnostic toolexperiencegenomic toolsneutrophilnovelnovel diagnosticspathogenrenal damageresponserestorationtick bitetool
项目摘要
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,是一个日益严重的问题
由于患病率增加和地理范围扩大,美国出现了这种情况。估计有30万
2017 年美国发生了 LD 病例。病程变化很大,可包括
器官特异性和播散性受累,伴有急性和慢性表现。存在知识差距
关于急性 LD 期间 Bb 在血液中传播过程中的免疫事件。我们的目标是
通过开发测量中性粒细胞与 Bb 相互作用的新工具来弥补这一知识差距
血。在前期工作中,我们证明了微流体测定用于研究宿主病原体的可行性
血液中的相互作用。具体来说,我们发现 (A) 尖峰后中性粒细胞自发运动表型为
血液中只有 100 个 Bb,(B) 急性 LD 患者的血液样本中存在相似的表型,以及 (C)
在与 Bb 的早期相互作用过程中,补体在血液中中性粒细胞的激活中发挥着关键作用。继续
通过这些努力,我们将优化中性粒细胞检测设计,以 (1) 研究中性粒细胞和中性粒细胞之间的相互作用
单细胞分辨率下活的、活动的 Bb (2) 识别中性粒细胞对 Bb 的标志性反应,以及 (3) 探测中继
少量 Bb 激活血液中的补体期间中性粒细胞的功能。我们将开始申请
在特异性抗体出现之前测量急性 LD 期间患者中性粒细胞功能的新工具
产生并在治疗期间评估血液中 Bb 的清除率。总的来说,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 反应的了解。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Daniel Irimia其他文献
Daniel Irimia的其他文献
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{{ truncateString('Daniel Irimia', 18)}}的其他基金
In vivo Monitoring of Neutrophil Function in Patients after Stem Cell Transplant
干细胞移植后患者中性粒细胞功能的体内监测
- 批准号:
10679553 - 财政年份:2023
- 资助金额:
$ 21万 - 项目类别:
Microfluidic Assessment of Clinical Outcomes in Preterm Newborns
早产儿临床结果的微流控评估
- 批准号:
10164831 - 财政年份:2017
- 资助金额:
$ 21万 - 项目类别:
Transient Obstruction of Capillary Networks by Chromatin Yarns from Neutrophils in Older Adults
老年人中性粒细胞染色质纱线对毛细血管网络的短暂阻塞
- 批准号:
8953369 - 财政年份:2015
- 资助金额:
$ 21万 - 项目类别:
Microfluidic tools for probing neutrophil reversed migration
用于探测中性粒细胞反向迁移的微流体工具
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9096701 - 财政年份:2015
- 资助金额:
$ 21万 - 项目类别:
Neutrophil Decision Making in Confined Environments in Health and Disease
健康和疾病中受限环境中的中性粒细胞决策
- 批准号:
9897528 - 财政年份:2010
- 资助金额:
$ 21万 - 项目类别:
Neutrophil Decision Making in Confined Environments in Health and Disease
健康和疾病中受限环境中的中性粒细胞决策
- 批准号:
10379440 - 财政年份:2010
- 资助金额:
$ 21万 - 项目类别:
Neutrophil Decision Making in Confined Environments in Health and Disease
健康和疾病中受限环境中的中性粒细胞决策
- 批准号:
7859917 - 财政年份:2010
- 资助金额:
$ 21万 - 项目类别:
Neutrophil Decision Making in Confined Environments in Health and Disease
健康和疾病中受限环境中的中性粒细胞决策
- 批准号:
8068338 - 财政年份:2010
- 资助金额:
$ 21万 - 项目类别:
Neutrophil Decision Making in Confined Environments in Health and Disease
健康和疾病中受限环境中的中性粒细胞决策
- 批准号:
8463563 - 财政年份:2010
- 资助金额:
$ 21万 - 项目类别:
Neutrophil Decision Making in Confined Environments in Health and Disease
健康和疾病中受限环境中的中性粒细胞决策
- 批准号:
8258312 - 财政年份:2010
- 资助金额:
$ 21万 - 项目类别:
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