The impact of infectious disease on cardiovascular leukocyte heterogeneity in mice

• Applicant: Privatdozent Dr. Friedrich Felix Hoyer
• Subject Area: Cardiology, Angiology ; Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 448821529

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.

• DFG Programme: Research Grants