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

Autor: Däullary T; Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, Germany.; Faculty of Biology, Biocenter, Chair of Microbiology, Julius-Maximilians-Universität Würzburg (JMU), Würzburg, Germany., Imdahl F; Helmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany., Dietrich O; Helmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany., Hepp L; Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, Germany., Krammer T; Helmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany., Fey C; Fraunhofer Institute for Silicate Research (ISC),Translational Center Regenerative Therapies (TLC-RT), Würzburg, Germany., Neuhaus W; Austrian Institute of Technology (AIT), Vienna, Austria.; Department of Medicine, Faculty of Medicine and Dentistry, Danube Private University (DPU), Krems, Austria., Metzger M; Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, Germany.; Fraunhofer Institute for Silicate Research (ISC),Translational Center Regenerative Therapies (TLC-RT), Würzburg, Germany.; Fraunhofer Institute for Silicate Research, Project Center for Stem Cell Process Engineering, Würzburg, Germany., Vogel J; Helmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.; Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany., Westermann AJ; Helmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.; Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany., Saliba AE; Helmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany., Zdzieblo D; Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, Germany.; Fraunhofer Institute for Silicate Research (ISC),Translational Center Regenerative Therapies (TLC-RT), Würzburg, Germany.; Fraunhofer Institute for Silicate Research, Project Center for Stem Cell Process Engineering, Würzburg, Germany.
Jazyk: angličtina
Zdroj: Gut microbes [Gut Microbes] 2023 Jan-Dec; Vol. 15 (1), pp. 2186109.
DOI: 10.1080/19490976.2023.2186109
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: