Cell polarity and host-pathogen interactions
Cellular polarity influences sensing of virus infection in intestinal epithelial cells
Epithelial cells are polarized with an apical side facing the lumen of the gut and a basolateral side facing the lamina propria. We are using both cell lines and organoid models to study how cell polarity influences host pathogen interactions. We are addressing how defect in both the polarized sensing of enteric pathogens and the polarized immune response generated by epithelial cells is linked to impairment of gut homeostasis ultimately leading to the development of inflammatory bowel diseases.
Human intestinal organoid
Molecular origins of polarized immune response in intestinal epithelial cells allowing them to partially tolerate apical commensals while remaining fully responsive to invasive basolateral pathogens.
Population context and intrinsic innate immune response
The heterogeneous response to interferons in epithelial cells is determined by the population context (i.e. a cell’s positions within a population) through cell polarization and basolateral localization of the interferon receptor.
Isogenic epithelial cells respond in a heterogeneous manner to type I and type III interferons.
The population context (position of a cell within a population) drives the heterogeneous response to interferons, with cells located at the edge of a population being more responsive than cells located in the center of a population.
Cells in the center of a population are refractive to interferon treatment from their apical side due to the polarized basolateral distribution of the interferon receptors.
By controlling the response to interferon treatment, the population context affects susceptibility to viral infections.
