Microbial Detection by Ixodes Scapularis Ticks

肩胛硬蜱的微生物检测

• 批准号: 10440408
• 负责人: Joao Pedra
• 金额: $ 41.88万
• 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/10440408
• 关键词: Address; Affect; Anaplasma phagocytophilum; Anaplasmosis; Arthropods; Bacteria; Binding; Biochemical; Black-legged Tick; Blood; Borrelia burgdorferi; CD36 gene; Cells; Competence; Complex; Detection; Enzymes; FADD protein; Golgi Apparatus; Homeostasis; Human; Immune; Immune signaling; Immune system; Immunity; Immunologics; Infection; Integration Host Factors; Interferon Type II; Interferons; Janus kinase; Laboratories; Life; Lipid Binding; Lipids; Lyme Disease; Mammals; Membrane; Membrane Fusion; Microbe; Molecular; Names; Nuclear; Order Spirochaetales; Pathogenesis; Pathway interactions; Pattern recognition receptor; Peptidoglycan; Phagocytosis; Phosphotransferases; Physiological; Proteins; Rickettsia; Role; STAT protein; Signal Transduction; Stat2 protein; Testing; Ticks; Tumor Necrosis Factor Receptor; granulocyte; human pathogen; in vivo; innovation; microbial; microbiota; novel; pathogen; pathogenic microbe; peptidoglycan recognition protein; receptor; response; ubiquitin-protein ligase; x-linked inhibitor of apoptosis protein

PROJECT 2: Microbial Detection by Ixodes scapularis Ticks Abstract: The Ixodes scapularis immune deficiency (IMD) pathway resembles the tumor necrosis factor receptor network in mammals and elicits a humoral response against the spirochete Borrelia burgdorferi and the rickettsial agent Anaplasma phagocytophilum – two distinct bacteria that cause Lyme disease and human granulocytic anaplasmosis, respectively. The Pedra laboratory recently proposed the existence of a functionally divergent IMD signaling cascade in ticks. We showed that the tick IMD network was activated in response to the lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), a component of bacterial inner membranes. Signaling relay in I. scapularis occurred in the absence of transmembrane peptidoglycan recognition proteins (PGRPs), Fas-associated protein with a death domain (FADD) and IMD, the adaptor molecule for which the immunological circuit was named. Interestingly, biochemical interactions proceeded between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme Bendless. For Project #2 in this P01 application, our central hypothesis states that the I. scapularis IMD pathway functions as a molecular rheostat impacting acquisition and persistence of B. burgdorferi and A. phagocytophilum. Aim#1 of this proposal will characterize the I. scapularis IMD pathway during pathogen infection. Aim#2 of this proposal will define a molecular crosstalk between the I. scapularis IMD signaling cascade and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, as there is increasing evidence that B. burgdorferi and A. phagocytophilum may be recognized by multiple pattern recognition receptors. Collectively, our findings will enable the detection of novel signaling hubs in tick- pathogen interactions and develop innovative scientific paradigms in microbial pathogenesis and arthropod immunity.

项目2：肩突硬蜱的微生物检测 翻译后摘要：肩突硬蜱免疫缺陷（IMD）途径类似于肿瘤坏死因子 哺乳动物和哺乳动物中的受体网络对伯氏疏螺旋体的体液应答， 立克次体病原体嗜吞噬细胞无形体-两种不同细菌，导致莱姆病和人类 粒细胞无形体病。佩德拉实验室最近提出， 功能发散IMD信号级联。我们发现蜱虫IMD网络在 对脂质1-棕榈酰-2-油酰-sn-甘油-3-磷酸甘油（POPG）的反应，POPG是细菌的一种组分， 内膜I中的信号继电器。肩胛肌在缺乏跨膜肽聚糖的情况下发生 识别蛋白（PGRP）、具有死亡结构域的Fas相关蛋白（FADD）和IMD（衔接子 免疫回路就是以这种分子命名的。有趣的是， X-连锁凋亡抑制蛋白（XIAP），E3泛素连接酶和E2结合酶之间 无穷无尽对于P01申请中的项目#2，我们的中心假设指出，I.肩胛肌IMD 途径作为影响B的获得和持续的分子变阻器发挥作用。burgdorferi和A. 嗜吞噬细胞菌本提案的目标1将体现I.肩胛肌IMD通路 感染本提案的目标#2将定义I.肩胛肌IMD信号 级联和Janus激酶/信号转导子和转录激活子（JAK/STAT）途径，因为 越来越多的证据表明，B。burgdorferi和A.嗜吞噬细胞菌可通过多种模式识别 识别受体总的来说，我们的研究结果将使检测新的信号枢纽蜱- 病原体相互作用，并在微生物发病机理和节肢动物 免疫力