Genetically Modifying Lactobacillus to Alter Gut Inflammation and Pathogens

该项目的重点是表征1型干扰素的表达， (IFN)并确定施用对照的后果， 转基因乳酸杆菌对葡聚糖硫酸钠诱导的肠道炎症的影响。我们成功 表明表达干扰素的细菌而不是对照细菌， 快速的STAT 1磷酸化，这种作用需要细菌和细胞之间的接触。 巨噬细胞此外，这种作用依赖于干扰素β受体，但它不依赖于干扰素β受体。 不需要收费接收器2或9。干扰素基因在乳酸杆菌中的表达 在原代小鼠树突状细胞以及小鼠中也诱导了STAT 1的快速磷酸化。 肠上皮细胞系我们还证明了转基因小鼠直接分泌IFN-β， 细菌目前关于细菌对DSS诱导的肠道炎症的影响的研究已经 结果好坏参半。虽然我们已经看到， 与对照细菌相比，转基因细菌对体重减轻的影响 小鼠对DSS诱导的结肠炎的反应是可变的。我们目前 努力的重点是确定这种变化的原因，以及确定关键的 用于评估转基因小鼠分泌的IFN的生物学效应的分子标记 细菌

This project has focused on characterizing the expression of the Type 1 interferon (IFN) by Lactobacillus and determining the consequences of administering control and transgenic Lactobacillus on dextran sodium sulfate induced gut inflammation. We successfully demonstrated that bacteria expressing the interferon but not the control bacteria, triggered rapid STAT1 phosphorylation and that this effect required contact between the bacteria and the macrophages. Furthermore, this effect was dependent on the interferon-beta receptor but did not require toll receptors 2 or 9. The expression of the interferon gene by the Lactobacillus also induced rapid STAT1 phosphorylation in primary murine dendritic cells as well as a mouse gut epithelial cell line. We also demonstrated direct secretion of IFN-beta by the transgenic bacteria. Current studies on the effects of the bacteria on DSS induced gut inflammation have yielded mixed results. While we have seen decreased blood in the intestines of mice treated with transgenic bacteria as compared to control bacteria, the effects on the weight loss experienced by the mice in response to the DSS induced colitis have been variable. Our current efforts are focused on defining the causes of this variability as well as identifying key molecular markers for assessing the biological effects of the IFN secreted by the transgenic bacteria.