Heart attacks and strokes often leave behind traces that extend far beyond the affected organ – and the immune system plays a surprisingly active role here. Still a young concept in immunology, trained immunity describes how the innate immune system develops a memory and can thus drive sustained inflammation processes after an injury. If this memory is dysregulated, it can fuel chronic systemic inflammation that affects distant organs. Although trained immunity was originally discovered in connection with infections, there is increasing evidence that sterile injuries like heart attacks and ischemic strokes can also trigger such prolonged changes to the immune system.

In his research, Arthur Liesz has already demonstrated that these injuries trigger epigenetic reprogramming in the stem and progenitor cells of the bone marrow. As a result, the immune system remains in a mode of persistent activation, which can worsen dysfunctions in other organs. With his expertise in the fields of immunology, neuroscience, cardiology, and clinical medicine and in the use of state-of-the-art technologies, Liesz now plans to systematically decipher the underlying mechanisms in his ERC project TRAINED (The Role of Trained Immunity in Brain-Body Communication and Secondary Organ Dysfunction).

Central to this undertaking are the following questions: How exactly does sterile tissue damage change the bone marrow niche? Which disease-specific patterns emerge in the process? And to what extent is dysregulated trained immunity actually responsible for secondary organ injury. At the same time, the project will assess what significance these processes have for human health. “With TRAINED, we aim to establish trained immunity as a central disease mechanism for sterile injuries and identify the molecular switches that drive multimorbidity,” says Liesz. “Ultimately, this will pave the way for novel therapies that prevent harmful immunological signals from an injured organ reaching and damaging other organs.”