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

• 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
• 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

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.

大部分关于吸入性炭疽的工作都集中在外毒素上。我们最近的研究 表明B肽聚糖组分。炭疽菌细胞壁诱导产生 炎性细胞因子和趋化因子。细胞因子和趋化因子的产生仅仅是 来自外周血单核细胞;淋巴细胞和中性粒细胞不应答。我们有初步的 正在进行的结构工作以化学表征B。炭疽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细胞外受体，并了解 由受体诱导的信号传导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，肽聚糖诱导单核细胞凋亡的亚群不同于 单核细胞产生炎性细胞因子。我们提出了一个实验计划，以确定机制 肽聚糖引发的细胞凋亡单核细胞凋亡可能与B的高死亡率有关。 炭疽和其他革兰氏阳性病原体的可能性，通过消除一个重要的组成部分， 先天免疫系统我们将通过用B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。