The interplay between antiviral responses and gut homeostasis

Responsabilité scientifique :

Carla Saleh

Partenariat :

Descriptif :

Gut epithelium is constantly exposed to changing environmental conditions including both
beneficial and pathogenic microorganisms. For orally acquired pathogens, as many insect
transmitted viruses, including arthropod-borne viruses, intestine epithelial cells represent the first
line of host defense. Intestine tissue constitutes not only a physical defense barrier but also a site
of active immune response to restrict pathogens invasion. This host-pathogen interplay causes
both damage and stress to the gut epithelium and disequilibrium on its homeostasis that can lead
to intestinal disease and even the tumorous lesions formation. It is known that during bacterial
infections, immune responses contribute to intestinal stem cell-mediated gut renewal. Works on
antiviral immune responses and homeostasis control on the gut epithelium during viral gut remain
scarce. Viruses can establish either acute infections or persistent infections on their hosts. During
acute infections, the virus replicates actively and, infection may result in clearance of the virus or
death of the host. Persistent infections, normally established in successful insect viral vectors, are
in long-lasting viral infections with minor fitness costs for the host. Our objective in this work
proposal is to understand the relationship between viral infections, midgut antiviral responses,
stem cell-mediated intestinal homeostasis and tumor formation. We aim also at deciphering how
host antiviral and homeostatic responses of midgut may determine the outcome of either persistent
or acute viral infections. To do so, we will combine the expertise of two partners excelling on
antiviral responses in insects (Partner 1, Carla Saleh, Institut Pasteur) and on the biology of the
midgut and its adult stem cell population (Partner 2, Allison Bardin, Institut Curie).