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

• 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
• 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

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.

总体 - 摘要 拟议的计划项目（P01），题为“蜱免疫信号、微生物群和获取 伯氏疏螺旋体和嗜吞噬细胞无形体”旨在通过以下方式了解其分子机制： 硬蜱免疫系统识别入侵的微生物，与常驻肠道微生物群相互作用， 我们发现了两种非正统的蜱免疫级联反应：(a) 在微生物识别中，通过间接“跨界”电路触发，该电路由在体内获得的哺乳动物细胞因子触发 载体血粉，或（b）通过非典型细菌脂质直接诱导 我们还确定了（c）蜱肠道微生物群与入侵的相互作用。 病原体影响媒介的生理和免疫，最终影响蜱虫感染伯氏疏螺旋体的能力。 以这些范例为基础，结合专业知识和资源。 来自四个在蜱传感染方面有着令人印象深刻的研究历史的机构，我们将确定如何 离散硬蜱蜱免疫途径，无论是独立还是协同，影响进入和 两种主要病原体的持续存在，即伯氏疏螺旋体和嗜吞噬细胞球菌，这些微生物构成了 由于其不同的结构和遗传特征以及不同的生活方式，我们建议的重点是 细胞外或细胞内 - 以及它们是最常见的蜱传感染的原因 在美国和欧洲许多地区，该计划项目拨款利用了特定的检测方法和工具。 以及我们实验室开发的方法，这些实验室有着悠久的富有成效的合作历史，以及 它将得到管理核心和蜱资源核心的支持，生物体和细胞 实现本 P01 目标的拟议目标是 1) 开发一个 Tick 核心 2) 确定哺乳动物如何 蜱血粉中存在的因素刺激多种跨物种免疫信号通路影响 3）通过信号传导研究蜱微生物检测的分子基础 4) 检查蜱免疫组和肠道之间的相互作用 微生物群以及这些事件如何影响蜱传病原体的持久性，该提案将。 增加我们对蜱免疫信号通路如何运作以及如何与免疫系统相互作用的基本了解 肠道微生物群影响多种蜱传病原体在载体中持续存在的能力，并随后 通过共享研究数据和资源来感染脊椎动物宿主。 科学界将播下创新研究的新种子，加深我们对蜱传疾病的了解 最后，随着技术和概念上的突破，P01将吸引新的消费者。 一代科学家参与并推进这一重要但被忽视的科学研究领域。

项目成果

Tick hemocytes have pleiotropic roles in microbial infection and arthropod fitness.

蜱血细胞在微生物感染和节肢动物适应性中具有多效性作用。

• 发表时间: 2023-09-03
• 作者: Rolandelli, Agustin;Laukaitis;Bogale, Haikel N;Singh, Nisha;Samaddar, Sourabh;O'Neal, Anya J;Ferraz, Camila R;Butnaru, Matthew;Mameli, Enzo;Xia, Baolong;Mendes, M Tays;Butler, L Rainer;Marnin, Liron;Cabrera Paz, Francy E;Vale
• 通讯作者: Vale

Genetic manipulation of an Ixodes scapularis cell line.

肩胛硬蜱细胞系的遗传操作。

• 发表时间: 2024-03-13
• 影响因子: 6.4
• 作者: Singh, Nisha;Rolandelli, Agustin;O'Neal, Anya J;Butler, L Rainer;Samaddar, Sourabh;Laukaitis;Butnaru, Matthew;Mohr, Stephanie E;Perrimon, Norbert;Pedra, Joao H F
• 通讯作者: Pedra, Joao H F

Specific mRNA lipid nanoparticles and acquired resistance to ticks.

特定的 mRNA 脂质纳米粒子并获得了对蜱的抵抗力。

• 发表时间: 2023-07-31
• 影响因子: 5.5
• 作者: Matias, Jaqueline;Cui, Yingjun;Tang, Xiaotian;Sajid, Andaleeb;Arora, Gunjan;Wu, Ming;DePonte, Kathleen;Muramatsu, Hiromi;Tam, Ying K;Narasimhan, Sukanya;Pardi, Norbert;Weissman, Drew;Fikrig, Erol
• 通讯作者: Fikrig, Erol

The role of Rab27 in tick extracellular vesicle biogenesis and pathogen infection.

Rab27 在蜱细胞外囊泡生物发生和病原体感染中的作用。

• 发表时间: 2024-02-09
• 影响因子: 3.2
• 作者: Butler, L Rainer;Singh, Nisha;Marnin, Liron;Valencia, Luisa M;O'Neal, Anya J;Paz, Francy E Cabrera;Shaw, Dana K;Chavez, Adela S Oliva;Pedra, Joao H F
• 通讯作者: Pedra, Joao H F

Acquired tick resistance: The trail is hot.

获得性蜱虫抵抗力：道路很热。

• 发表时间: 2021
• 影响因子: 2.2
• 作者: Narasimhan, Sukanya;Kurokawa, Cheyne;DeBlasio, Melody;Matias, Jaqueline;Sajid, Andaleeb;Pal, Utpal;Lynn, Geoffrey;Fikrig, Erol
• 通讯作者: Fikrig, Erol