The impact of infectious disease on cardiovascular leukocyte heterogeneity in mice

传染病对小鼠心血管白细胞异质性的影响

• 批准号: 448821529
• 负责人: Privatdozent Dr. Friedrich Felix Hoyer
• 金额: --
• 依托单位: Klinik III für Innere Medizin: Kardiologie, Angiologie, Pneumologie und internistische Intensivmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/448821529?language=en
• 关键词: impact; infectious; disease; cardiovascular; leukocyte

Bacterial infections markedly increase the risk for subsequent cardiovascular events. The propensity for cardiac sequelae is not limited to the infection’s acute phase but persists for a prolonged time. Cell types mediating risk storage and molecular mechanisms contributing to or aggravating cardiovascular disease after infection remain insufficiently understood. Recent work demonstrated profound transcriptional and numerical responses of tissue-resident macrophages to remote injury in various organs. We aim to explore whether alterations in the innate immune system’s landscape relay the elevated risk for cardiovascular events after infection. We will characterize numerical changes of cardiovascular and circulating myeloid cells in different infectious disease mouse models. Cell dynamics and mechanisms of cell expansion such as proliferation will be analyzed by flow cytometry and fate mapping experiments. RNA sequencing experiments will be used to determine leukocyte heterogeneity and profile transcriptional changes in myeloid cells. Finally, we will explore functional consequences of bacteremia-induced alterations in different cardiovascular mouse models. Nanoparticle-enabled RNAi will be used to assess relevance of target genes in-vivo. The proposed experiments may help to identify previously unknown mechanisms of risk storage after bacterial infection.

细菌感染显著增加随后心血管事件的风险。心脏后遗症的倾向不仅限于感染的急性期，而且会持续很长时间。介导风险储存的细胞类型和感染后导致或加重心血管疾病的分子机制仍然没有得到充分的了解。最近的工作表明，组织驻留的巨噬细胞在各种器官的远程损伤深刻的转录和数字响应。我们的目的是探索先天免疫系统景观的改变是否会导致感染后心血管事件风险的升高。我们将描述不同感染性疾病小鼠模型中心血管和循环髓系细胞的数量变化。将通过流式细胞术和命运图谱实验分析细胞动力学和细胞扩增机制（如增殖）。RNA测序实验将用于确定白细胞异质性和骨髓细胞中的转录变化谱。最后，我们将探讨不同心血管小鼠模型中菌血症诱导的改变的功能后果。纳米粒子使能的RNAi将用于评估体内靶基因的相关性。拟议的实验可能有助于确定细菌感染后风险储存的先前未知机制。