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Microbial Detection by Ixodes Scapularis Ticks

肩胛硬蜱的微生物检测

基本信息

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
项目类别：
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

项目摘要

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：肩胛骨蜱微生物检测