Depending on how an antigen is perceived dendritic cells (DCs) can mature in a homeostatic or immunogenic manner. While pathogen-associated molecules are known to trigger immunogenic maturation through activation of TLRs, the signals driving homeostatic DC maturation have long remained enigmatic. Recently, our lab uncovered that apoptotic cell engulfment and subsequent changes in intracellular cholesterol levels appear critical to drive homeostatic maturation of cDC1s, one of the two major DC subsets. cDC1s are also essential for cross-presentation of viral antigens derived from engulfed virus-infected cells. Uptake of virus-infected cells will also cause changes in intracellular cholesterol levels and we wondered whether and how changes in cholesterol metabolism affect immunogenic maturation programs. Novel technologies such as CITE-Seq combined with trajectory algorithms will be used to obtain an in depth-view of transcriptional programs driving maturation processes in splenic DCs. This will be complemented with functional validation using different genetic mouse models. A thorough understanding of the differences between homeostatic versus immunogenic maturation processes in DCs is not only relevant from a fundamental perspective, but besides highly needed in context of tumor biology or vaccination strategies, where novel markers able to distinguish tolerogenic versus immunogenic DC are urgently requested.