A Multicellular In Vitro Model of the Human Intestine with Immunocompetent Features Highlights Host-Pathogen
Spyridon Damigos1, Aylin Caliskan2, Gisela Wajant1
1Department for Functional Materials in Medicine and Dentistry, University Hospital Würzburg, Würzburg, Germany.
Researchers developed a 3D human intestinal model with immune cells to study enteric infections. This innovative model mimics human tissue, offering a promising alternative to animal testing for understanding Salmonella Typhimurium (STm) interactions.
Area of Science:
- Microbiology
- Immunology
- Tissue Engineering
Background:
- Studying enteric pathogen infections at the tissue level is challenging due to limitations in current human intestinal models and the variability of animal models.
- Incorporating immune cells, such as macrophages, into human epithelial tissue models is difficult but crucial for mimicking native tissue immunocompetence.
Purpose of the Study:
- To establish a 3D immunocompetent tissue model of the human small intestine.
- To investigate the interactions between Salmonella enterica serovar Typhimurium (STm) and the human intestinal model.
- To explore the potential of this model as an alternative to animal experimentation for studying enteric infections.
Main Methods:
- Development of a 3D human intestinal tissue model using decellularized submucosa enriched with monocyte-derived macrophages (MDMs).
- Incorporation of MDMs to create an immunocompetent model that recapitulates in vivo-like cellular diversity.
- Infection studies using STm to analyze pathogen-tissue interactions, immune cell responses, and epithelial cell behavior.
Main Results:
- The 3D model successfully mimicked in vivo-like cellular diversity, including the induction of microfold (M) cells.
- STm was observed to interact physically with M-like cells, and MDMs demonstrated trans-epithelial migration and phagocytosis of STm.
- STm infection induced inflammatory cytokine levels and led to the shedding of infected epithelial cells, suggesting an intracellular reservoir.
Conclusions:
- The developed 3D immunocompetent human intestinal model provides a valuable platform for studying enteric bacterial infections.
- This model effectively recapitulates key aspects of host-pathogen interactions, including M-cell involvement and immune responses.
- The 3D model shows significant potential as a human-specific alternative to animal models for enteric infection research.
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