期刊
BIOMATERIALS
卷 220, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119396
关键词
Microphysiological system; Gut-on-chip; Microbiota; Mucosal immunity; Candida albicans; Lactobacilli
资金
- Deutsche Forschungsgemeinschaft (DFG) [CRC/TR124 FungiNet, CRC 1278 PolyTarget]
- Deutsche Forschungsgemeinschaft (DFG) through Cluster of Excellence Balance of the Microverse - Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC 2051 [390713860]
- German Ministry for Education and Research (BMBF) [01EO1002]
- Alexander von Humboldt postdoctoral research fellowship
- European Commission through Marie Sklodowska-Curie Actions (MSCA) Innovative Training Network EUROoC [812954]
- Marie Curie Actions (MSCA) [812954] Funding Source: Marie Curie Actions (MSCA)
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.
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