A primary cell-based in vitro model of the human small intestine reveals the induction of OLFM4 expression as host cell response during Salmonella Typhimurium infection

Infection research largely relies on classical cell culture or mouse studies; both having limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models. As the replication of biological and physico-chemical properties of the host tissue is of high importance in this context, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Further, using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our generated model for modern infection research in the human context. Infection assays coupled to spatio-temporal readouts provided evidence that the key steps of epithelial infection by the pathogen could be reconstructed in our model. Interestingly, we detected the upregulation of Olfactomedin-4 in infected cells, a previously unknown host cell response upon Salmonella infection. Analysis of two replicates of the human intestinal tissue model via 10x Genomics 3'Gene expression. Multiplexing via Biolegend TotalSeqA Hashtags. Hashtag1 = Replicate1; Hashtag2 = Replicate2