Organoids and derived models to study the microenvironments of bacterial infections

The microenvironment of an infection is the biological space surrounding the interaction between the pathogen and the host. Focusing on epithelial barriers, the apical microenvironment corresponds to the lumen of the organ, where the pathogen must survive amidst body fluids, microbiota, and cellular secretions. On the opposite side, the basal microenvironment includes stromal cells, endothelial cells of blood vessels, and immune cells recruited to combat infection. The first distinguishing element between the apical and basal domains is the epithelium itself, which consists of polarized cells that secrete different molecules to their apical and basal domains. Organoids and other stem cell-derived culture systems have emerged as valuable models for studying epithelial barriers and their capacities for pathogen recognition, inflammatory signalling, and differentiation. By mimicking multiple aspects of epithelial biology in vitro, organoids provide an opportunity to investigate infections from the initial attack to the subsequent defences. This review explores how organoids, stem cell-derived planar cultures, and micro-physiological systems are transforming our understanding of infection microenvironments.