The impact of infectious disease on cardiovascular leukocyte heterogeneity in mice

细菌感染显著增加随后发生心血管事件的风险。心脏后遗症的倾向并不局限于感染的急性期，而是持续很长时间。介导风险储存的细胞类型和导致或加重感染后心血管疾病的分子机制仍未得到充分了解。最近的研究表明，组织内巨噬细胞对各种器官的远端损伤有深刻的转录和数值反应。我们的目的是探索先天免疫系统的改变是否介导了感染后心血管事件风险的增加。我们将描述不同传染病小鼠模型中心血管和循环骨髓细胞的数值变化。细胞动力学和细胞增殖等机制将通过流式细胞术和命运图谱实验进行分析。RNA测序实验将用于确定骨髓细胞的白细胞异质性和转录变化。最后，我们将在不同的心血管小鼠模型中探讨菌血症诱导的改变的功能后果。纳米颗粒激活RNAi将用于评估体内靶基因的相关性。提出的实验可能有助于确定以前未知的细菌感染后风险储存机制。

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.