Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin

摘要: Genetically encoded antibiotic peptides are evolutionarily ancient and widespread effector molecules of immune defence. Mammalian defensins, one subset such peptides, have been implicated in the antimicrobial defence capacity phagocytic leukocytes various epithelial cells, but direct evidence magnitude their vivo effects not clearly demonstrated. Paneth specialized epithelia small intestinal crypt, secrete abundant alpha-defensins other polypeptides including human defensin 5 (HD-5; also known as DEFA5). Although activity HD-5 has demonstrated vitro, functional studies biology limited by lack models. To study role HD-5, we developed a transgenic mouse model using 2.9-kilobase minigene containing two exons 1.4 kilobases 5'-flanking sequence. Here show that expression these mice is specific to cells reflects endogenous enteric gene expression. The storage processing matches observed humans. were markedly resistant oral challenge with virulent Salmonella typhimurium. These findings provide support for critical epithelial-derived defensins mammalian host