Multifactorial Immune Cell-Based Development of Heart Failure

The development of heart failure is a complex and multifactorial process. Risk factors such as prior viral cardiac infection and hypertension identify individuals at risk of developing heart failure, and the current literature has conflicting evidence about the role of individual cardiac immune cell subsets in these pathologies. Some of the contradictory results stem from the fact that immune cells within the myocardium have been characterized only superficially. In addition, the interaction between different risk factors, while clinically important, has been ignored at the basic science level. In this thesis, we first specifically define an important, yet uninvestigated cardiac immune subset â the dendritic cell (DC). We show the myocardium contains two specific conventional DC lineages (CD103+ and CD11b+), that possess unique, tissue-specific and lineage-specific mechanisms that regulate their life cycle and tissue residency. We identified cardiac CD103+ DCs as critical in inducing antigen-specific CD8+ T cell responses following subclinical viral myocarditis, and preventing the development of heart failure. In addition, chronic hypertension also predisposes mice to develop heart failure following subclinical viral myocarditis, highlighting that only by combining two risk factors, does heart failure develop.M.Sc.2019-01-10 00:00:0