An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii.

Autor: Zhang J; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. j.zhang6@uva.nl.; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands. j.zhang6@uva.nl.; Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, Location Academic Medical Center, Amsterdam, the Netherlands. j.zhang6@uva.nl., Huang YJ; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Trapecar M; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Wright C; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Schneider K; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Kemmitt J; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Hernandez-Gordillo V; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Yoon JY; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Mechanical Engineering, Yonsei University, Seoul, South Korea., Poyet M; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Institute of Experimental Medicine, University of Kiel, Kiel, Germany., Alm EJ; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Breault DT; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Trumper DL; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Griffith LG; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. griff@mit.edu.; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. griff@mit.edu.; Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, MA, USA. griff@mit.edu.
Jazyk: angličtina
Zdroj: NPJ biofilms and microbiomes [NPJ Biofilms Microbiomes] 2024 Mar 29; Vol. 10 (1), pp. 31. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1038/s41522-024-00501-z
Abstrakt: Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4 + naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4 + naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined populations of immune cells in the gut microphysiological system demonstrated the usefulness of GuMI physiomimetic platform to study microbe-epithelial-immune interactions in healthy and disease conditions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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