Modulation of Peritoneal Macrophage Differentiation and Function for Prophylaxis of Complications in Decompensated Cirrhosis

• Applicant: Professor Dr. Tony Bruns
• Subject Area: Gastroenterology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 272135177

In decompensated cirrhosis small intestinal bacterial overgrowth, intestinal permeability and disturbed antimicrobial capacity contribute to increased translocation of bacteria and bacterial products into the peritoneal cavity. Whereas the gastrointestinal barrier constitutes the first line of defense, peritoneal immune function is the crucial second line of defense to prevent spontaneous bacterial peritonitis. Resident macrophages comprise a key population of innate immune cells and fulfill specialized functions regarding recognition and phagocytosis of microbial pathogens, antigen presentation, induction and resolution of inflammation as well as recruitment and activation of other immune cells. This proposal aims at investigating to which extent bacterial translocation is associated with a specific phenotype of the peritoneal macrophage population characterized by increased pro-inflammatory cytokine production, endotoxin tolerance, reduced phagocytic capability and increased numbers of immature, recently recruited monocytes, and therefore contributes to peritoneal immune deficiency, peritonitis, and aggravated systemic inflammation. Defining pathological differentiation of peritoneal macrophages in decompensated cirrhosis will identify molecular mechanisms allowing non-antibiotic targeted prophylaxis of complications of bacterial translocation at the peritoneal level.

• DFG Programme: Research Grants