Modeling host-microbe interactions in immunocompetent engineered human gut tissues
Description
As a primary port of pathogen entry, the intestinal mucosa has developed a sophisticated set of defenses to ward off infections. Investigating the human-specific intestinal barrier responses to pathogens is limited by the lack of models integrating the necessary architectural complexity with an autologous immune compartment. Here, we developed engineered barrier models of the human small intestine and colon combining a multilineage epithelium, mucus layer, accessible microbial compartment, and autologous tissue-resident immune cells. These tissues recapitulate morphological and functional properties that are region-specific and compare to those of the native organ. We use the model to characterize the human epithelial response to Salmonella Typhimurium at the single-cell level, uncovering the distinct gene regulatory networks that underpin luminal versus intracellular pathogen presence. Invaded epithelial cells initiate an IL-18 signaling axis that triggers cytotoxic T-cell activation, resulting in epithelial shedding and barrier disruption. Overall, this work allows for the modular integration of epithelial, microbial, and immune compartments providing a versatile system for studying human intestinal physiology and pathologies. This repository contains the processed single cell data of engineered tissues and tissue reference with cell type annotation, statistically significant differentially accessible chromatin regions upon S.Tm infection and TF-target regulomes inferred by Pando based on the S.Tm infection dataset.
Files
Steps to reproduce
Please refer to the Method of the "Modeling host-microbe interactions in immunocompetent engineered human gut tissues" (López-Sandoval, Harter, Yu et al) and github repository (https://github.com/devsystemslab/Host-microbe_interaction_model/)