TY  - JOUR
A1  - Däullary, Thomas
A1  - Imdahl, Fabian
A1  - Dietrich, Oliver
A1  - Hepp, Laura
A1  - Krammer, Tobias
A1  - Fey, Christina
A1  - Neuhaus, Winfried
A1  - Metzger, Marco
A1  - Vogel, Jörg
A1  - Westermann, Alexander J.
A1  - Saliba, Antoine-Emmanuel
A1  - Zdzieblo, Daniela
T1  - A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection
JF  - Gut Microbes
N2  - 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 in vitro. Here, 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. Using the foodborne pathogen Salmonella enterica 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 Salmonella 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.
KW  - intestinal enteroids
KW  - biological scaffold
KW  - Salmonella Typhimurium
KW  - OLFM4
KW  - NOTCH
KW  - filamentous Salmonella Typhimurium
KW  - bacterial migration
KW  - bacterial virulence
KW  - 3D tissue model
KW  - olfactomedin 4
KW  - infection
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350451
VL  - 15
IS  - 1
ER  -