1. A three-dimensional immunocompetent intestine-on-chip model as in vitro platform for functional and microbial interaction studies.
- Author
-
Maurer M, Gresnigt MS, Last A, Wollny T, Berlinghof F, Pospich R, Cseresnyes Z, Medyukhina A, Graf K, Gröger M, Raasch M, Siwczak F, Nietzsche S, Jacobsen ID, Figge MT, Hube B, Huber O, and Mosig AS
- Subjects
- Antigens, CD metabolism, Biomarkers metabolism, Caco-2 Cells, Cadherins metabolism, Cell Membrane Permeability drug effects, Cell Movement drug effects, Colony Count, Microbial, Cytokines metabolism, Epithelial Cells drug effects, Epithelial Cells metabolism, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells ultrastructure, Humans, Intestines immunology, Lacticaseibacillus rhamnosus drug effects, Lacticaseibacillus rhamnosus physiology, Lipopolysaccharides pharmacology, Microvilli drug effects, Microvilli metabolism, Models, Biological, Perfusion, Zonula Occludens-1 Protein metabolism, Immunocompetence drug effects, Intestines microbiology, Lab-On-A-Chip Devices, Microbial Interactions drug effects
- Abstract
Alterations of the microbial composition in the gut and the concomitant dysregulation of the mucosal immune response are associated with the pathogenesis of opportunistic infections, chronic inflammation, and inflammatory bowel disease. To create a platform for the investigation of the underlying mechanisms, we established a three-dimensional microphysiological model of the human intestine. This model resembles organotypic microanatomical structures and includes tissue resident innate immune cells exhibiting features of mucosal macrophages and dendritic cells. The model displays the physiological immune tolerance of the intestinal lumen to microbial-associated molecular patterns and can, therefore, be colonised with living microorganisms. Functional studies on microbial interaction between probiotic Lactobacillus rhamnosus and the opportunistic pathogen Candida albicans show that pre-colonization of the intestinal lumen of the model by L. rhamnosus reduces C. albicans-induced tissue damage, lowers its translocation, and limits fungal burden. We demonstrate that microbial interactions can be efficiently investigated using the in vitro model creating a more physiological and immunocompetent microenvironment. The intestinal model allows a detailed characterisation of the immune response, microbial pathogenicity mechanisms, and quantification of cellular dysfunction attributed to alterations in the microbial composition., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF