权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum

蜱免疫信号传导、微生物群以及伯氏疏螺旋体和嗜吞噬细胞无形体的获得

基本信息

批准号：
10440404
负责人：
Erol Fikrig
金额：
$ 153.75万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-13 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10440404
关键词：
Address Anaplasma phagocytophilum Anaplasmosis Area Biological Biological Assay Black-legged Tick Blood Borrelia burgdorferi CRISPR/Cas technology Cell Line Cells Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Communities Data Detection Development Europe Event Fostering Future Generations Genetic Goals Homeostasis Human Human Resources Immune Immune response Immune signaling Immune system Immunity Immunobiology Immunologic Deficiency Syndromes In Vitro Infection Ingestion Institution Instruction Invaded Investigation Ixodes Janus kinase Knowledge Laboratories Life Style Lipids Lyme Disease Membrane Methodology Microbe Molecular Organism Pathway interactions Physiology Plants Prevalence Program Research Project Grants Reagent Recording of previous events Reporter Research Resources Role STAT protein Scientist Seeds Shapes Signal Pathway Signal Transduction Tick-Borne Infections Ticks Training United States Vector-transmitted infectious disease cytokine data resource extracellular genomic platform gut microbiota in vivo innovation microbial microbiota mouse model neglect outreach pathogen programs tick feeding tick-borne pathogen tool vector

项目摘要

OVERALL - Abstract The proposed Program Project (P01), entitled “Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum” aims to understand the molecular mechanisms by which the Ixodes tick immune system recognizes invading microbes, interfaces with resident gut microbiota, and impact pathogen persistence. We discovered two unorthodox tick immune cascades that are (a) involved in microbial recognition by an indirect “cross-kingdom” circuit triggered by a mammalian cytokine acquired in the vector blood meal, or (b) by a direct induction by specific bacterial lipids through an atypical immunodeficiency pathway. We also established that (c) interactions between tick gut microbiota and invading pathogens shape vector physiology and immunity, ultimately impacting the ability of ticks to acquire B. burgdorferi or A. phagocytophilum. Building on these paradigms and by combining the expertise and resources from four institutions with impressive history of research involving tick-borne infections, we will determine how discrete Ixodes tick immune pathways, either independently or synergistically, influence the entry and persistence of two major pathogens, B. burgdorferi and A. phagocytophilum. These microbes constitute the focus of our proposal due to their diverse structural and genetic features, their different lifestyles - either extracellular or intracellular - and the fact that they are responsible for the most prevalent tick-borne infections in the United States and many parts of Europe. This Program Project Grant leverages specific assays, tools and methodologies developed by our laboratories, who have a long history of productive collaboration, and which will be supported by an Administrative Core, and a Tick Resource Core whereby organisms and cell lines will be shared. The proposed aims to achieve the goals of this P01 are 1) Develop a Tick Core that provides the research reagents to all projects and to scientific community; 2) Determine how mammalian factors present in tick blood meal stimulate multiple cross-species immunity signaling pathways impacting persistence of diverse pathogens; 3) Investigate molecular basis of microbial detection in ticks via signaling relays and crosstalk by multiple immune pathways; 4) Examine interactions between tick immunome and gut microbiota and how these events impact persistence of tick-borne pathogens. Altogether, this proposal will increase our fundamental understanding of how tick immune signaling pathways operate and interface with the gut microbiota to influence the ability of diverse tick-borne pathogens to persist in the vector and subsequently infect the vertebrate host. The outreach activities generated by sharing the research data, and resources to the scientific community will plant new seeds of innovative research furthering our knowledge of tick-borne infections. Finally, with the technical and conceptual breakthroughs expected, the P01 will entice a new generation of scientists to be engaged and advance this important, yet neglected field of scientific research.

整体-摘要拟议方案项目(P01)，题为“壁虱免疫信号、微生物区系和获取伯氏疏螺旋体和吞噬细胞无浆体“的目的是通过硬蜱免疫系统识别入侵的微生物，与驻留的肠道微生物区系相互作用，并影响病原体的持久性。我们发现了两个非正统的壁虱免疫级联反应在微生物识别中，由一种哺乳动物细胞因子触发的间接“跨王国”回路载体血粉，或(B)由特定细菌脂通过非典型肺炎病毒直接诱导免疫缺陷途径。我们还证实了(C)壁虱肠道微生物区系与入侵之间的相互作用病原体塑造了媒介生理和免疫，最终影响到扁虱感染B。伯格多费氏杆菌或吞噬细胞性弧菌。在这些范例的基础上，通过结合专业知识和资源从四个有着令人印象深刻的扁虱传播感染研究历史的机构中，我们将确定独立的或协同的，离散的硬蜱免疫途径，影响进入和两种主要病原体--伯氏杆菌和吞噬细胞芽孢杆菌的持久性。这些微生物构成了我们建议的重点是由于他们不同的结构和基因特征，他们不同的生活方式- 细胞外或细胞内--它们是最流行的壁虱传播感染的罪魁祸首在美国和欧洲的许多地方。该计划项目赠款利用特定的分析、工具和由我们的实验室开发的方法，他们有着长期的富有成效的合作历史，以及它将得到一个管理核心和一个扁虱资源核心的支持，生物和细胞线路将共享。为实现本P01的目标，建议的目标是1)开发一个滴答核心，为所有项目和科学界提供研究试剂；2)确定哺乳动物如何壁虎血粉中存在的因子可刺激多种跨物种免疫信号通路不同病原体的持久性；3)通过信号研究扁虱微生物检测的分子基础通过多条免疫途径传递和串扰；4)检查扁虱免疫体和肠道之间的相互作用微生物区系以及这些事件如何影响壁虱传播病原体的持久性。总而言之，这项提议将增加我们对壁虱免疫信号通路如何运作以及如何与肠道微生物区系影响不同的扁虱传播病原体在媒介中持续存在的能力并随后感染脊椎动物的宿主。通过共享研究数据和资源而产生的外展活动科学界将播下创新研究的新种子，进一步加深我们对壁虱传播的认识。感染。最后，随着技术和概念的突破预期，P01将吸引一个新的一代科学家致力于并推进这一重要但被忽视的科学研究领域。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector.

DOI：
10.1128/iai.00426-20
发表时间：
2020-11-16
期刊：
Infection and immunity
影响因子：
3.1
作者：
Cao Y;Rosen C;Arora G;Gupta A;Booth CJ;Murfin KE;Cerny J;Marin Lopez A;Chuang YM;Tang X;Pal U;Ring A;Narasimhan S;Fikrig E
通讯作者：
Fikrig E

Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies.

DOI：
10.1016/j.vaccine.2021.11.003
发表时间：
2021-12-20
期刊：
Vaccine
影响因子：
5.5
作者：
Matias J;Kurokawa C;Sajid A;Narasimhan S;Arora G;Diktas H;Lynn GE;DePonte K;Pardi N;Valenzuela JG;Weissman D;Fikrig E
通讯作者：
Fikrig E

Acquired tick resistance: The trail is hot.

获得蜱虫抗药性：踪迹炙手可热。