This project aims to develop a new therapeutic approach targeting the interaction between mitochondrial DNA (mtDNA) and the innate immune system, namely complement and Toll-like receptors (TLR). mtDNA is released from injured cells and induces sterile inflammation in diseases like e.g. cardiac arrest, trauma and transplantation. We aim to test the hypothesis that mtDNA and the complement system augment each other’s effects and thus sterile inflammation in a vicious circle; mtDNA activates complement and complement activation releases mtDNA from cells. The major aim of the project is to (i) reveal the mechanism behind mtDNA-complement system/TLR interaction and (ii) break this vicious circle.