Yersina perstis interactions with macrophages

鼠疫是一种新出现的传染病，在包括北 和南美洲，是国家生物防御的首要任务。研究致病性耶尔森氏菌， 细菌负责鼠疫，提供了有价值的见解发病机制和进化。 耶尔森氏菌属和广泛鼠疫耶尔森氏菌的基因组测序 从青铜时代到现在，为这一研究提供了丰富的资源。 鼠疫感染的一个显著特征是细菌复制时缺乏炎症 网站.最近对肺鼠疫的研究揭示了一个两阶段的过程： 随着疾病的进展，反应随后是高度炎症阶段。在初始 阶段，非人灵长类动物和小鼠模型显示无细胞浸润。细胞外 Y的存在。灵长类动物肺部的鼠疫不会引发炎症。在一个淋巴腺癌的大鼠模型中， 鼠疫，中性粒细胞浸润到引流淋巴结延迟，感染部位发生 坏死而不是炎症。Y. pseudotuberculosis和Y.鼠疫 感染表明中性粒细胞募集，但感染的遏制不充分。 对III型分泌系统和其他毒力因子的研究已经探索了它们在 中和早期炎症反应。然而，了解巨噬细胞极化 在鼠疫早期阶段仍然不完整。一个中心假设认为Y.鼠疫 通过抑制M1极化或诱导M2巨噬细胞来预防炎症 这些机制将增强巨噬细胞极化如何有助于早期 鼠疫中的免疫抑制，防止多形核白细胞的浸润 （PMNs）和促进鼠疫的初始抗炎阶段。 目标1。鼠疫菌暴露于阻断剂后巨噬细胞极化的研究 炎症通过抑制M1极化或诱导M2巨噬细胞。 目标二。确定诱导的信号通路和Y使用的机制。鼠疫， 影响巨噬细胞极化。 目标3。检测Y.从鼠疫菌到巨噬细胞

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.