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

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。

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.