A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection
ABSTRACTInfection 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 Engineer...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2186109 |
| _version_ | 1797236645278253056 |
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| author | Thomas Däullary Fabian Imdahl Oliver Dietrich Laura Hepp Tobias Krammer Christina Fey Winfried Neuhaus Marco Metzger Jörg Vogel Alexander J. Westermann Antoine-Emmanuel Saliba Daniela Zdzieblo |
| author_facet | Thomas Däullary Fabian Imdahl Oliver Dietrich Laura Hepp Tobias Krammer Christina Fey Winfried Neuhaus Marco Metzger Jörg Vogel Alexander J. Westermann Antoine-Emmanuel Saliba Daniela Zdzieblo |
| author_sort | Thomas Däullary |
| collection | DOAJ |
| description | ABSTRACTInfection 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. |
| first_indexed | 2024-03-11T14:20:17Z |
| format | Article |
| id | doaj.art-4e6314defbf542fa8797bca5587d5316 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-24T17:07:09Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-4e6314defbf542fa8797bca5587d53162024-03-28T22:38:20ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2023.2186109A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infectionThomas Däullary0Fabian Imdahl1Oliver Dietrich2Laura Hepp3Tobias Krammer4Christina Fey5Winfried Neuhaus6Marco Metzger7Jörg Vogel8Alexander J. Westermann9Antoine-Emmanuel Saliba10Daniela Zdzieblo11Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, GermanyHelmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyHelmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, GermanyHelmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyFraunhofer Institute for Silicate Research (ISC),Translational Center Regenerative Therapies (TLC-RT), Würzburg, GermanyAustrian Institute of Technology (AIT), Vienna, AustriaChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, GermanyHelmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyHelmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyHelmholtz-Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, GermanyChair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg (UKW), Würzburg, GermanyABSTRACTInfection 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.https://www.tandfonline.com/doi/10.1080/19490976.2023.2186109Intestinal enteroidsbiological scaffoldSalmonella TyphimuriumOLFM4NOTCHfilamentous Salmonella Typhimurium |
| spellingShingle | Thomas Däullary Fabian Imdahl Oliver Dietrich Laura Hepp Tobias Krammer Christina Fey Winfried Neuhaus Marco Metzger Jörg Vogel Alexander J. Westermann Antoine-Emmanuel Saliba Daniela Zdzieblo A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection Gut Microbes Intestinal enteroids biological scaffold Salmonella Typhimurium OLFM4 NOTCH filamentous Salmonella Typhimurium |
| title | A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection |
| title_full | A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection |
| title_fullStr | A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection |
| title_full_unstemmed | A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection |
| title_short | A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection |
| title_sort | primary cell based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to salmonella typhimurium infection |
| topic | Intestinal enteroids biological scaffold Salmonella Typhimurium OLFM4 NOTCH filamentous Salmonella Typhimurium |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2186109 |
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