Impact of TRAIL on the immune system in peritonitis

• Applicant: Professorin Dr. Katharina Beyer
• Subject Area: General and Visceral Surgery
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 374319388

In addition to interactions with tumour cells, there is growing evidence that TRAIL also interacts with cells of the immune system. Thereby, TRAIL appears to act as a double-edged sword interacting with the cells of the innate as well as the adaptive immune system.Thus, TRAIL-treatment highly significantly improved survival in a murine model of peritonitis. In this context, granulocytes were crucial for the effect of TRAIL. Whereas the amount of granulocytes within the septic lymphoid organs was decreased following TRAIL-treatment, the fraction of apoptotic granulocytes was significantly increased within these organs. However, the amount of granulocytes within the peritoneum was increased following TRAIL-treatment resulting in an improved peritoneal function.In parallel, TRAIL-/- mice were more affected within the early course of peritonitis when compared to respective wild-type mice. In marked contrast, within the later course of peritonitis, sepsis severity was decreased in TRAIL-/- mice resulting in an improved overall survival. Results from other peritonitis models provided evidence that TRAIL-expressing CD8 cells might be crucial for this effect.The goal of the present project is to further explore the impact of TRAIL on the course of peritonitis thereby examining interactions of TRAIL with granulocytes as well as the influence of TRAIL-expressing CD8 cells on the immune system. These experiments will shed light on the impact of TRAIL on the immune system and rule out implications for the treatment of peritonitis.

• DFG Programme: Research Grants