Regulation of Skin Immunity by a Tick Bite
蜱虫叮咬对皮肤免疫的调节
基本信息
- 批准号:10514626
- 负责人:
- 金额:$ 19.31万
- 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:2021-11-01 至 2024-10-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnestheticsAnimal ModelAnimalsAnti-Inflammatory AgentsAnticoagulantsApplications GrantsArbovirusesArchitectureAreaArthropodsBacteriaBar CodesBiogenesisBiological AssayBiologyBiopsyBiteBlack-legged TickBloodCastor Bean TickCattleCaviaCell CommunicationCell SeparationCellsChromosome MappingCommunitiesCoupledDermalDermisDiseaseEmerging TechnologiesEnvironmentEpidermisEtiologyEuropeFermentationFlow CytometryFutureGene Expression ProfilingHemostatic AgentsHistologyHomeostasisHumanImmuneImmune responseImmunityImmunobiologyImmunology procedureInflammationInterventionKnowledgeLaboratoriesLiteratureMammalsMeasuresMediatingMolecularMolecular AnalysisMusN-ethylmaleimide-sensitive proteinOrganoidsParasitesPopulationPropertyProteinsRNARNA InterferenceReagentReceptor GeneRegulationResearchResearch PersonnelResistanceResourcesRoleSalivaSalivarySalivary GlandsSalivary ProteinsSeminalSiteSkinSystemT-LymphocyteTechnologyTherapeuticThinkingTick-Borne DiseasesTicksTravelUnited StatesVirusWorkacquired immunityarthropod-borneextracellular vesiclesfascinatefeedingfollow-upfootfunctional plasticityimmunoregulationinsightinterspecies communicationkeratinocytemicrobialnanovesicleneglectnew technologypathogenreceptorsingle-cell RNA sequencingtick bitetick feedingtick salivatick transmissiontooltranscriptomicstransmission processvectorvesicular releasewound healingγδ T cells
项目摘要
Summary/Abstract: Ticks transmit bacteria, viruses and parasites that cause disease in humans and other
animals. This phenomenon is partly due to the secretion of redundant and pluripotent salivary proteins that
disrupt host homeostasis and alter inflammation upon blood-feeding. Recently, extracellular vesicles, a
heterogenous population of nanovesicles that mediate interspecies communication, were shown to facilitate
pathogen transmission to mammals. We developed a tick salivary organoid system that mimics extracellular
vesicle release. We also manipulated the biogenesis of tick extracellular vesicles by silencing the expression
of N-ethylmaleimide-sensitive factor attachment receptor (SNARE) genes through RNA interference. Finally,
we provided causality to our findings by showing that tick extracellular vesicles affect resident dendritic
epidermal T cells (DETCs) in the skin. How immune cells are targeted by tick nanovesicles in the skin remains
unsettled. Whether tick extracellular vesicles have functional plasticity during interspecies relationships
remains elusive. In this R21 application, we will explore the central hypothesis that tick extracellular vesicles
provide an advantageous skin immune environment for Ixodes scapularis feeding via the DETC-keratinocyte
axis. DETCs interact with keratinocytes, which comprise approximately 95% of the skin epidermal layer. In Aim
#1 of this proposal, we will determine whether the effect of I. scapularis extracellular vesicles on DETCs is
direct or indirect. We will use single cell RNA sequencing coupled with animal models devoid of DETCs to
evaluate the directionality of the skin immune response during a tick bite. In Aim #2 of this grant proposal, we
will ascertain the architecture of the skin when the biogenesis of tick extracellular vesicles is disrupted. We will
measure the immune response of DETCs through skin biopsies via flow cytometry coupled with cell sorting,
microbial stimulation and spatial transcriptomics. Spatial transcriptomics combines traditional histology
information with single cell gene expression analysis and positional barcoding. Thus, we will construct an
architectural map of genes associated with DETCs and keratinocytes during a tick bite. Collectively, this R21
project will underscore the importance of ticks as arthropods of
摘要/摘要:蜱传播细菌、病毒和寄生虫,导致人类和其他动物疾病。
动物这种现象部分是由于分泌的多余和多能唾液蛋白,
破坏宿主体内平衡并改变血液喂养后的炎症。最近,细胞外囊泡,
介导种间通讯的纳米囊泡的异质群体被证明有助于
病原体传播给哺乳动物我们开发了一种蜱唾液类器官系统,
囊泡释放。我们还操纵了蜱细胞外囊泡的生物合成,
N-乙基马来酰亚胺敏感因子附着受体(SNARE)基因的RNA干扰。最后,
我们提供了因果关系,我们的研究结果表明,蜱细胞外囊泡影响居民树突状细胞,
表皮T细胞(DETC)。皮肤中的蜱纳米囊泡如何靶向免疫细胞仍然存在
不安蜱类细胞外囊泡在种间关系中是否具有功能可塑性
仍然难以捉摸在这个R21应用程序中,我们将探讨蜱细胞外囊泡的中心假设,
通过DETC-角质形成细胞为肩胛硬蜱的摄食提供有利的皮肤免疫环境,
轴线DETC与角质形成细胞相互作用,角质形成细胞占皮肤表皮层的约95%。在Aim中
#1这个建议,我们将确定是否影响我。肩胛肌细胞外囊泡对DETC是
直接或间接。我们将使用单细胞RNA测序结合缺乏DETC的动物模型,
评估蜱虫叮咬期间皮肤免疫反应的方向性。在本补助金提案的目标#2中,我们
将确定当蜱细胞外囊泡的生物发生被破坏时皮肤的结构。我们将
通过流式细胞术结合细胞分选通过皮肤活检测量DETC的免疫应答,
微生物刺激和空间转录组学。空间转录组学结合了传统的组织学
通过单细胞基因表达分析和位置条形码化提供信息。因此,我们将构建一个
蜱叮咬期间与DETC和角质形成细胞相关的基因的结构图。总的来说,R21
该项目将强调蜱虫作为节肢动物的重要性,
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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Joao Pedra其他文献
Joao Pedra的其他文献
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{{ truncateString('Joao Pedra', 18)}}的其他基金
The Tick Immune Response During Microbial Infection
微生物感染期间的蜱免疫反应
- 批准号:
10621853 - 财政年份:2015
- 资助金额:
$ 19.31万 - 项目类别:
Ubiquitylation and Rickettsial Colonization of a Tick Vector
蜱载体的泛素化和立克次体定植
- 批准号:
9188063 - 财政年份:2015
- 资助金额:
$ 19.31万 - 项目类别:
The Tick Immune Response During Microbial Infection
微生物感染期间的蜱免疫反应
- 批准号:
10291359 - 财政年份:2015
- 资助金额:
$ 19.31万 - 项目类别:
The Tick Immune Response During Microbial Infection
微生物感染期间的蜱免疫反应
- 批准号:
10414128 - 财政年份:2015
- 资助金额:
$ 19.31万 - 项目类别:
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