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

调节腹膜巨噬细胞分化和功能以预防失代偿性肝硬化并发症

• 批准号: 272135177
• 负责人: Professor Dr. Tony Bruns
• 金额: --
• 依托单位: Klinik für Gastroenterologie, Stoffwechselerkrankungen und Internistische Intensivmedizin (Med. Klinik III)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/272135177?language=en
• 关键词: Modulation; Peritoneal; Macrophage; Differentiation; Function

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.

在失代偿性肝硬化小肠细菌过度生长，肠道通透性和干扰的抗菌能力有助于增加细菌和细菌产物转移到腹膜腔。而胃肠道屏障构成的第一道防线，腹膜免疫功能是至关重要的第二道防线，以防止自发性细菌性腹膜炎。驻留巨噬细胞包括先天免疫细胞的关键群体，并且实现关于微生物病原体的识别和吞噬、抗原呈递、炎症的诱导和消退以及其他免疫细胞的募集和活化的专门功能。该提案旨在研究细菌易位在何种程度上与腹膜巨噬细胞群体的特定表型相关，其特征在于促炎性细胞因子产生增加、内毒素耐受性、吞噬能力降低和未成熟、最近招募的单核细胞数量增加，因此导致腹膜免疫缺陷、腹膜炎和全身性炎症加重。确定失代偿期肝硬化患者腹腔巨噬细胞的病理分化，将有助于确定非抗生素靶向预防腹膜水平细菌移位并发症的分子机制。