Role of bactericidal permeability increasing protein (BPI) in bidirectional hostmicrobiota communication in the gut

点击翻译按钮获取中文摘要

Bactericidal permeability increasing protein (BPI) has been characterized as LPS-binding protein with the highest affinity and displays strong antimicrobial activities against Gram negative bacteria. BPI is expressed by myeloid hematopoietic cells such as neutrophils and by epithelial cells including those of the gastrointestinal tract. Besides its features as very potent endogenous antibiotic, recent studies have shown that BPIneutralizing autoantibodies as well as BPI gene polymorphisms (Lys216Glu) are associated with inflammatory bowel diseases (IBD, Crohn´s disease and ulcerative colitis). We aim to investigate the role of BPI for stabilizing the interrelationship of gut microbiota and the gastrointestinal mucosal surface in homoeostatic and inflammatory conditions. Applying newly generated BPI gene-deficient as well as BPI-humanized BAC-transgenic mice I) the influence of microbiota on the mucosal expression of BPI as well as II) the role of BPI for shaping the microbiota composition, III) their spatial segregation from the host mucosa and IV) the control of bacteria-driven inflammatory processes in the gut will be addressed. A better understanding of the role of BPI in the bidirectional microbiota-host interaction will provide the basis for future therapeutic strategies in inflammatory bowel diseases.