Abstract

Innate immune cells, such as macrophages and dendritic cells, inhabit all body organs to detect danger and initiate immune responses as well as to maintain organ health. However, the mechanisms facilitating those diverse functions of innate immune cells in distinct tissue milieus are poorly understood.

Recently, we found tissue macrophages to engage their mitochondrial metabolism in an organ-specific manner. Mechanistically, they adapt the activity of their mitochondrial electron transport chain to handle large amounts of environmental lipids in homeostasis. This functional dependence of tissue macrophages on mitochondrial metabolism can be harnessed to ameliorate obesity-related pathologies. On the other hand, innate immune cells have to quickly respond to insults and activate immunity for containment, in particular conventional dendritic cells. We discovered a differential bioenergetic dependence of the immunogenic responsiveness of type 1 versus type 2 dendritic cells (unpublished data). The distinct engagement of mitochondrial metabolism regulates the epigenetic state and functional outputs of dendritic cell subsets and affects their potency to induce anti-cancer immunity.

Overall, my talk will focus on how mitochondria and an active electron transport chain regulate the context-dependent functions of innate immune cells via entirely distinct molecular mechanisms.