Genetically Modifying Lactobacillus to Alter Gut Inflammation and Pathogens

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This project is new and this past year was focused on characterizing the expression of the Type 1 interferon (IFN) by Lactobacillus. An in vitro assay was developed whereby bacteria expressing the mouse interferon-beta gene were added directly to a mouse macrophage cell line and the phosphorylation of STAT1 was measured after 30 minutes to 1 hour of incubation. 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. Furthermore, it appeared to alter the expression of interleukin-1 beta (IL-1beta) by murine dendritic cells. Current studies are focused on determining if the Lactobacillus have any effects on dextran sodium sulfate induced gut inflammation in mouse model systems.