Lay summary
The gut combines and integrates very different physiological functions required for maintaining the equilibrium of the whole organism. In addition to its role in digestion, it is the main entry route for pathogens, and a reservoir for resident bacteria that must be tolerated. Finally, the intestinal epithelium undergoes a constant renewal required to maintain the integrity of this barrier. However, little is known about how these functions are regulated and coordinated, or what mechanisms are required to ensure gut homeostasis upon exposure to external challenges such as bacterial infection.
In recent years, Drosophila has emerged as a powerful model to dissect host-pathogen interactions, leading to the paradigm of antimicrobial peptide regulation by the Toll and Imd signaling pathways. The strength of this model is due to the availability of powerful and cost effective genetic and genomic tools, as well as its high degree of similarity to vertebrate innate immunity. Using an integrated approach, our goal will be to study the mechanisms that make the gut an efficient and interactive
barrier despite its constant interactions with microbes. We will also focus our attention on the regulatory mechanisms that restore normal gut function upon challenge with bacteria. This project will utilize integrated approaches to dissect not only the gut immune response, but also gut homeostasis and physiology in the presence of microbiota, as well as strategies used by entomopathogens to circumvent these defenses. We believe that the fundamental knowledge generated on Drosophila gut immunity will serve as a paradigm of epithelial immune reactivity and have broader impacts on our comprehension of animal immune defense mechanisms and gut homeostasis.