B. anthracis Peptidoglycan as a Pro-inflammatory Agent in Anthrax Pathogenesis

B. 炭疽杆菌肽聚糖作为炭疽发病机制中的促炎剂

基本信息

批准号：
7695608
负责人：
Kenneth Mark Coggeshall
金额：
$ 28.55万
依托单位：
OKLAHOMA MEDICAL RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7695608
关键词：
Actins Adverse effects Animal Model Anthrax disease Antibiotic Therapy Apoptosis Bacillus anthracis Bacillus anthracis spore Bacteria Binding Biological Biological Process Biology Blood Breathing Cause of Death Cell Death Cell Wall Cells Cerebrospinal Fluid Cessation of life Chemicals Data Digestion Disaccharides Disease Elements Epithelial Cells Equipment Event Exotoxins Exposure to Funding General Population Goals Health Human IL8 gene Immune Immune system Immunologics Individual Infection Inflammation Inflammatory Laboratories Left Life Ligands Link Liquid Chromatography Lymphocyte MAP Kinase Gene MAPK14 gene Mass Spectrum Analysis Measurement Measures Mediating Membrane Potentials Mitochondria Modeling Molecular Morbidity - disease rate Muramidase Nucleotides Organ Organism Papio Pathogenesis Pathway interactions Patients Pattern recognition receptor Peptides Peptidoglycan Phenotype Phospho-Specific Antibodies Phosphotransferases Pleural effusion disorder Polymers Polysaccharides Production Proteins RIPK2 gene Reproduction spores Rodent Role Sepsis Serum Signal Transduction Structure Surface Testing Toll-Like Receptor 2 Toll-like receptors Vaccines Vertebral column Work caspase-8 caspase-9 chemokine cytokine exposed human population extracellular improved inhibitor/antagonist milliliter mitochondrial membrane monocyte mortality neutrophil nonhuman primate novel outcome forecast pathogen peptidoglycan receptor peripheral blood polymerization prevent receptor receptor binding response small molecule stem tool

项目摘要

Much of the work on inhalation anthrax has exclusively focused on the exotoxins. Our recent studies ndicate that the peptidoglycan component of the B. anthracis cell wall induces the production of nflammatory cytokines and chemokines. The production of the cytokines and chemokines is exclusively from peripheral blood monocytes; lymphocytes and neutrophils do not respond. We have preliminary and on-going structural work to chemically characterize B. anthracis peptidoglycan. We have novel tools to identify the currently unknown extracellular receptor for Gram-positive peptidoglycan and to understand the signaling events induced by the receptor and causing the changes in monocyte biology. Additionally, we have new data indicating that peptidoglycan induces monocyte apoptosis in a subpopulation distinct from the monocytes producing inflammatory cytokines. We present an experimental plan to identify the mechanism of peptidoglycan-triggered apoptosis. The monocyte apoptosis might contribute to the high mortality of B. anthracis and possibly of other Gram-positive pathogens by eliminating an important component of the innate immune system. We will test this possibility by challenging rodents and non-human primates with B. anthracis peptidoglycan and measuring monocyte levels.

吸入炭疽的大部分工作仅集中在外毒素上。我们最近的研究表明炭疽芽孢杆菌细胞壁的肽聚糖成分诱导产生炎症细胞因子和趋化因子。细胞因子和趋化因子的产生完全是来自外周血单核细胞；淋巴细胞和中性粒细胞没有反应。我们有初步的持续的结构工作以化学特征炭疽杆菌肽聚糖。我们有新的工具确定目前未知的革兰氏阳性肽聚糖的细胞外受体，并了解受体引起的信号事件并引起单核细胞生物学的变化。另外，我们有新的数据表明肽聚糖在不同的亚群中诱导单核细胞凋亡产生炎症细胞因子的单核细胞。我们提出了一个实验计划，以识别机制肽聚糖触发的凋亡。单核细胞凋亡可能有助于B的高死亡率。炭疽病以及其他革兰氏阳性病原体可能通过消除重要组成部分先天免疫系统。我们将通过与B一起挑战啮齿动物和非人类灵长类动物来测试这种可能性。炭疽肽聚糖和测量单核细胞水平。