Pedicord Virginia A, Lockhart Ainsley A K, Rangan Kavita J, Craig Jeffrey W, Loschko Jakob, Rogoz Aneta, Hang Howard C, Mucida Daniel
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, NY, USA.
Sci Immunol. 2016 Sep;1(3). doi: 10.1126/sciimmunol.aai7732. Epub 2016 Sep 22.
Commensal intestinal bacteria can prevent pathogenic infection; however, limited knowledge of the mechanisms by which individual bacterial species contribute to pathogen resistance has restricted their potential for therapeutic application. Here, we examined how colonization of mice with a human commensal protects against enteric infections. We show that improves host intestinal epithelial defense programs to limit serotype Typhimurium pathogenesis in multiple models of susceptibility. protection is mediated by a unique peptidoglycan hydrolase, SagA, and requires epithelial expression of pattern recognition receptor components and antimicrobial peptides. Ectopic expression of SagA in non-protective and probiotic bacteria is sufficient to enhance intestinal barrier function and confer resistance against Typhimurium and pathogenesis. These studies demonstrate that specific factors from commensal bacteria can be used to improve host barrier function and limit the pathogenesis of distinct enteric infections.
肠道共生菌可预防病原体感染；然而，对于单个细菌物种促进抗病原体能力的机制了解有限，限制了它们在治疗应用中的潜力。在此，我们研究了用一种人类共生菌定殖小鼠如何预防肠道感染。我们表明，在多种易感性模型中，它可改善宿主肠道上皮防御程序，以限制鼠伤寒血清型菌株的发病机制。这种保护作用由一种独特的肽聚糖水解酶SagA介导，并且需要模式识别受体成分和抗菌肽的上皮表达。在非保护性细菌和益生菌中异位表达SagA足以增强肠道屏障功能，并赋予对鼠伤寒菌株和发病机制的抗性。这些研究表明，共生菌的特定因子可用于改善宿主屏障功能，并限制不同肠道感染的发病机制。
