The Tick Immune Response During Microbial Infection

微生物感染期间的蜱免疫反应

• 批准号: 10414128
• 负责人: Joao Pedra
• 金额: $ 64.89万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414128
• 关键词: Address; Affect; Anaplasma phagocytophilum; Anaplasmosis; Applications Grants; Arachnida; Area; Arthropod Vectors; Arthropods; Babesia microti; Babesiosis; Basic Science; Biochemical; Bioenergetics; Bioinformatics; Biology; Black-legged Tick; Borrelia burgdorferi; Borrelia miyamotoi; Cell Wall; Cells; Cholesterol; Communicable Diseases; Communities; Coupling; Ensure; Enzymes; Europe; FADD protein; Funding; Genes; Genome; Gram-Negative Bacteria; Health; Hemocytes; Human; Immune; Immune response; Immune signaling; Immune system; Immunity; Immunobiology; Immunology; Infection; Infectious Disease Immunology; Insecta; Ixodes; Knowledge; Laboratories; Lead; Life; Life Cycle Stages; Life Style; Ligands; Lipids; Lipopolysaccharides; Longevity; Lyme Disease; Lysine; Mammals; Metabolic; Metabolism; Microbe; Molecular; Monoclonal Antibodies; Nuclear; Order Spirochaetales; Organism; Pathway interactions; Pattern; Peer Review; Peptidoglycan; Phylogeny; Physiology; Population; Powassan virus; Process; Proteins; Public Health; Publications; Resources; Rickettsia; Role; Signal Pathway; Signal Transduction; Textbooks; Tick-Borne Diseases; Tick-Borne Encephalitis; Tick-Borne Relapsing Fever; Ticks; Tumor Necrosis Factor Receptor; United States; Vector-transmitted infectious disease; arthropod-borne; cost effective; fitness; flexibility; granulocyte; hematophagy; infancy; interest; member; microbial; microbial colonization; novel; pathogen; peptidoglycan recognition protein; receptor; scaffold; screening; single-cell RNA sequencing; ubiquitin-protein ligase; vector; vector tick; x-linked inhibitor of apoptosis protein

The tick Ixodes scapularis transmits several pathogens of relevance to public health, including Borrelia burgdorferi (Lyme disease), Anaplasma phagocytophilum (human granulocytic anaplasmosis), B. miyamotoi (tick-borne relapsing fever), Babesia microti (babesiosis) and Powassan virus (tick-borne encephalitis). To date, while diverse areas of immunity have been studied in insects, the underpinnings of the tick immune system are in its infancy, and the molecules involved in microbial sensing remain chiefly undefined. Similarly, the molecular characterization of tick immune cells or hemocytes remains mostly elusive. Over the previous funding period, we discovered a non-canonical immune deficiency (IMD) network in I. scapularis and showed that the IMD pathway is important against B. burgdorferi and A. phagocytophilum infection. Specifically, we uncovered the role of molecules that act on the I. scapularis IMD pathway and provided mechanistic support for an observation that the immune system of ticks is fundamentally different than insects. We made substantial progress in addressing the three specific aims, which resulted in several peer-reviewed publications. For this R01 project (competing renewal), we will build on our earlier findings and investigate the nexus between metabolism and immunology. Our central hypothesis states that changes in metabolic status impact the immune system and microbial infection of ticks. Accordingly, in Aim #1 of this proposal, we will characterize the signaling flexibility of the IMD pathway in ticks. The classical textbook definition of an immune pathway consists of a fixed stack of proteins that amplifies the immune signal from a receptor to an effector. We will reveal that the tick IMD pathway is malleable and reprograms itself upon metabolic changes and/or microbial infection. In Aim #2 of this grant application, we will categorize tick hemocyte populations under distinct metabolic and microbial conditions through a platform that involves coupling of single cell RNA sequencing (scRNA-seq) with a monoclonal antibody screening strategy. This major resource to the vector biology community will show that metabolism and microbial infection affect tick hemocyte biology. In Aim #3 of this submission, we will assess whether metabolism affects fitness parameters associated with the life cycle of I. scapularis. We will also evaluate transstadial and transgenerational passage of microbes in ticks. Altogether, this R01 project will demonstrate that bioenergetic processes likely define cost-effective and/or energetically expensive tick-microbe interactions.

tick ixodes肩cap骨传播了几种与公共卫生相关的病原体， 包括Borrelia burgdorferi（莱姆病），Anaplasma phapocytophilum（人粒细胞 肿瘤病），B。宫本B. （tick传播脑炎）。迄今 tick免疫系统的基础处于其起步阶段，并且参与微生物感应的分子 主要是不确定的。同样，tick免疫细胞或血细胞的分子表征仍然存在 主要难以捉摸。在过去的资金期间，我们发现了非典型免疫缺陷（IMD） I. capularis中的网络，并表明IMD途径对B. burgdorferi和A. 吞噬细胞感染。具体而言，我们发现了作用于肩capularis imd的分子的作用 途径并为观察到tick的免疫系统是从根本上看的，提供了机械支持 与昆虫不同。我们在解决这三个特定目标方面取得了重大进展，这导致了 几个同行评审的出版物。对于这个R01项目（竞争续约），我们将建立在早期的基础上 发现并研究了代谢与免疫学之间的联系。我们的中心假设指出 代谢状态的变化会影响壁虱的免疫系统和微生物感染。因此，在目标＃1中 在此提案中，我们将表征tick中IMD途径的信号灵活性。古典教科书 免疫途径的定义由固定的蛋白质组成 效应子的受体。我们将揭示tick式IMD途径可延展并重新编程 代谢变化和/或微生物感染。在本赠款应用程序的AIM＃2中，我们将对tick进行分类 通过涉及的平台，在不同的代谢和微生物条件下的血细胞种群 单细胞RNA测序（SCRNA-SEQ）与单克隆抗体筛选策略的耦合。这 媒介生物学社区的主要资源将表明代谢和微生物感染会影响tick虫 血细胞生物学。在此提交的目标＃3中，我们将评估代谢是否影响健身参数 与肩cap骨的生命周期有关。我们还将评估跨性别和跨代通道 tick中的微生物。总之，这个R01项目将证明生物能过程可能定义成本效益 和/或能量昂贵的tick虫相互作用。