Microbial Detection by Ixodes Scapularis Ticks

肩胛硬蜱的微生物检测

• 批准号: 10222518
• 负责人: Joao Pedra
• 金额: $ 38.63万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222518
• 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; Structure; 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：肩部硬蜱的微生物检测 摘要：肩部硬蜱免疫缺陷(IMD)途径类似于肿瘤坏死因子。 在哺乳动物中的受体网络，并诱导对伯氏疏螺旋体和 立克次体病原体-吞噬细胞无形体-两种不同的细菌，导致莱姆病和人类 粒细胞性无浆体。佩德拉实验室最近提出了一种存在 在扁虱中，不同的IMD信号级联反应。我们发现Tick IMD网络在 对细菌的一种成分--脂蛋白1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol的反应 内膜。在没有跨膜肽聚糖的情况下，肩胛肌中的信号传递发生了 识别蛋白(PGRP)、带有死亡结构域的Fas相关蛋白(FADD)和适配器IMD 免疫回路以其命名的分子。有趣的是，生物化学相互作用 X连锁的凋亡抑制蛋白(XIAP)，一种E3泛素连接酶和E2结合酶之间的关系 无穷无尽。对于P01申请中的项目#2，我们的中心假设是肩周肌IMD 途径起到分子变阻器的作用，影响伯氏杆菌和A. 吞噬细胞性。目的：本研究的目的1将描述病原菌引起的肩周肌IMD途径。 感染。该提案的目的#2将定义肩胛肌IMD信号之间的分子串扰 CASCADE和Janus激酶/信号转导和转录激活因子(JAK/STAT)途径，就像存在的那样 越来越多的证据表明，伯氏杆菌和吞噬细胞性弧菌可能是通过多种模式识别的 识别受体。总而言之，我们的发现将使我们能够在TICK- 病原菌相互作用和发展微生物发病机制和节肢动物的创新科学范式 豁免权。