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：ixodes scapularis tick的微生物检测 摘要：ixodes肩cap骨免疫缺陷（IMD）途径类似于肿瘤坏死因子 哺乳动物中的受体网络，并引起针对螺旋体玻璃体伯氏菌的体液反应和 立克剂的齿状吞噬吞噬 - 两种不同的细菌，引起莱姆病和人类 粒细胞性肿瘤病。 Pedra实验室最近提出了 在功能上发散的IMD信号传导级联在壁虱中。我们证明了tick imd网络已激活 对脂质1-甲米酰-2-烯酰基-SN-甘油-3-磷酸甘油（POPG）的反应，这是细菌的成分 内膜。 I.肩cap骨的信号继电器发生在没有跨膜胡椒糖的情况下 识别蛋白（PGRP），与死亡结构域（FADD）和IMD的FAS相关蛋白（适配器） 免疫电路的分子。有趣的是，生化互动进行了 凋亡蛋白（XIAP），E3泛素连接酶和E2共轭酶之间的X连锁抑制剂之间 无弯。对于该P01应用程序中的项目2，我们的中心假设指出。 途径充当分子的变阻器，影响B. burgdorferi和A.的持久性。 吞噬细胞。该提案的目标＃1将表征病原体期间的I. scapularis IMD途径 感染。该提案的目标＃2将定义I. scapularis IMD信号之间的分子串扰 Cascade和Janus激酶/信号换能器和转录激活因子（JAK/STAT）途径，因为有 越来越多的证据表明，B. burgdorferi和A. phagocytophilum可以通过多种模式识别 识别受体。总的来说，我们的发现将使在tick中检测新的信号集线器。 病原体相互作用并在微生物发病机理和节肢动物中发展创新的科学范例 免疫。