A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection

• Published in: Gut microbes Vol. 15; no. 1; p. 2186109
• Main Authors: Däullary, Thomas, Imdahl, Fabian, Dietrich, Oliver, Hepp, Laura, Krammer, Tobias, Fey, Christina, Neuhaus, Winfried, Metzger, Marco, Vogel, Jörg, Westermann, Alexander J, Saliba, Antoine-Emmanuel, Zdzieblo, Daniela
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2023; Taylor & Francis Group
• Subjects: biological scaffold; Brief Report; filamentous Salmonella Typhimurium; Gastrointestinal Microbiome; Humans; Intestinal enteroids; Intestine, Small; NOTCH; OLFM4; Salmonella Infections, Animal; Salmonella Typhimurium; olfactomedin 4; biological scaffold; bacterial virulence; infection; Salmonella Typhimurium; NOTCH; 3D tissue model; Intestinal enteroids; OLFM4; bacterial migration; filamentous Salmonella Typhimurium
• ISSN: 1949-0976; 1949-0984
• DOI: 10.1080/19490976.2023.2186109

Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models . Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an model of the human small intestinal epithelium exhibiting -like characteristics. Using the foodborne pathogen serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.