Yersina perstis interactions with macrophages

鼠疫，一种新出现的传染病，流行于包括北方在内的多个大陆 和南美，是国家生物防御的重中之重。研究致病耶尔森氏菌， 负责鼠疫的细菌，为发病机制和进化提供了有价值的见解。 耶尔森氏菌属基因组测序及广泛分布的鼠疫耶尔森菌基因组 从青铜时代到现在，为这方面的研究提供了丰富的资源。 鼠疫感染的一个明显特征是细菌复制时没有炎症。 网站。最近对肺鼠疫的研究揭示了一个两阶段的过程：迟发性炎症 随着疾病的进展，紧随其后的是高度炎症阶段。在最初 阶段，非人类灵长类动物和小鼠模型显示没有细胞渗透。胞外 灵长类动物肺部存在鼠疫杆菌不会引发炎症。在腺瘤大鼠模型中 鼠疫，中性粒细胞向引流淋巴结的渗透延迟，感染部位经历 是坏死而不是炎症。假结核杆菌与鼠疫耶尔森菌的比较 感染表现为中性粒细胞聚集，但对感染的遏制不充分。 对III型分泌系统和其他毒力因子的研究探索了它们在 中和早期的炎症反应。然而，理解巨噬细胞极化 在鼠疫早期阶段仍未完成。一个中心假说表明，鼠疫杆菌 通过抑制M1极化或诱导M2巨噬细胞来预防炎症 这些机制将加强对巨噬细胞极化如何在早期 抑制鼠疫免疫，防止多形核白细胞的渗入 (PMN)和促进鼠疫的初始抗炎阶段。 目的1.研究鼠疫耶尔森氏菌阻断暴露后巨噬细胞的极化 通过抑制M1极化或诱导M2巨噬细胞的炎症。 目的2.确定鼠疫耶尔森氏菌诱导的信号通路及其作用机制 影响巨噬细胞极化。 目的3.检测鼠疫杆菌用来极化巨噬细胞的毒力因子。

Plague, an emerging infectious disease endemic to multiple continents, including North and South America, is a top priority in national biodefense. Studying pathogenic yersiniae, the bacteria responsible for plague, provides valuable insights into pathogenesis and evolution. Genomic sequencing of the Yersinia genus and extensive Yersinia pestis genomes spanning from the Bronze Age to the present offer a rich resource for this research. A distinct feature of plague infections is the lack of inflammation at bacterial replication sites. Recent studies on pneumonic plague reveal a two-phase course: a delayed inflammatory response followed by a highly inflammatory phase as the disease progresses. In the initial phase, non-human primate and mouse models show no cellular infiltration. Extracellular presence of Y. pestis in primate lungs does not trigger inflammation. In a rat model of bubonic plague, neutrophil infiltration into draining lymph nodes is delayed, and infected sites undergo necrosis instead of inflammation. Comparisons between Y. pseudotuberculosis and Y. pestis infections demonstrate neutrophil recruitment but inadequate containment of the infection. Research on the type III secretion system and other virulence factors has explored their role in neutralizing early inflammatory responses. However, understanding macrophage polarization during early plague stages remains incomplete. A central hypothesis suggests that Y. pestis prevents inflammation by inhibiting M1 polarization or inducing M2 macrophages Investigating these mechanisms will enhance knowledge of how macrophage polarization contributes to early immune suppression in plague, preventing the infiltration of polymorphonuclear leukocytes (PMNs) and promoting the initial anti-inflammatory stage of plague. Aim 1. Investigate macrophage polarization after Yersinia pestis exposure to block inflammation by either inhibiting M1 polarization or inducing M2 macrophages. Aim 2. Determine signaling pathways induced and mechanisms used by Y. pestis to influence macrophage polarization. Aim 3. Examine the virulence factors utilized by Y. pestis to polarize macrophages.