Genetically Modifying Lactobacillus to Alter Gut Inflammation and Pathogens

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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.