Clinician scientist-Programm 2025

Thema: "Systematic analysis of the role of the inflammasome and NETosis in sepsis-associated and - independent organ failure"

Zusammenfassung:
A dysregulated hast response to infection can lead to sepsis, a life-threatening condition that results in organ failure (1). The kidneys are among the organs most affected, leading to sepsis-associated acute kidney injury (SA-AKI). Sepsis-associated immune dysregulation is characterized by the coexistence of hyperinflammatory responses and immunosuppression. lmmunosuppression summarizes heterogeneous scenarios of an inadequate immune response to invading pathogens, which can affect both innate and adaptive immunity (2). However, how and which components ofthe immune response play a major role in sepsis-associated organ failure remains poorly understood. The inflammasome is an important part of the innate immune arsenal and plays a crucial role in the immune response to severe infections and trauma. Dysregulation of the inflammasome has been suggested to contribute to the pathology of severe infections, including COVID-19, and to sepsis-associated organ failure. Similarly, the dysregulated action of neutrophil extracellular traps (NETs), which serve as rapid immunological means to mitigate and contain infection, has been implicated in the pathogenesis of sepsis and kidney disease (3), but the underlying mechanisms are unknown. Here, 1 propose a systematic analysis of the role of inflammasome and NET dysfunction in sepsis-dependent or -independent organ failure and associated immune suppression in a clinical trial