An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii
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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2024
|
| Online Access: | https://hdl.handle.net/1721.1/154888 |
| _version_ | 1824457896653488128 |
|---|---|
| author | Zhang, Jianbo Huang, Yu-Ja Trapecar, Martin Wright, Charles Schneider, Kirsten Kemmitt, John Hernandez-Gordillo, Victor Yoon, Jun Young Poyet, Mathilde Alm, Eric J. Breault, David T. Trumper, David L. Griffith, Linda G. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Zhang, Jianbo Huang, Yu-Ja Trapecar, Martin Wright, Charles Schneider, Kirsten Kemmitt, John Hernandez-Gordillo, Victor Yoon, Jun Young Poyet, Mathilde Alm, Eric J. Breault, David T. Trumper, David L. Griffith, Linda G. |
| author_sort | Zhang, Jianbo |
| collection | MIT |
| description | 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 <jats:italic>Faecalibacterium prausnitzii/Faecalibacterium duncaniae</jats:italic> with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4<jats:sup>+</jats:sup> 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 <jats:italic>F. prausnitzii</jats:italic> (GuMI-APC-FP), <jats:italic>F. prausnitzii</jats:italic> increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (<jats:italic>TLR1</jats:italic>) and interferon alpha 1 (<jats:italic>IFNA1</jats:italic>) 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<jats:sup>+</jats:sup> naive T cells (GuMI-APCT-FP), <jats:italic>TLR1</jats:italic>, <jats:italic>IFNA1</jats:italic>, and <jats:italic>IDO1</jats:italic> transcription levels decreased with a simultaneous increase in <jats:italic>F. prausnitzii</jats:italic>-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 <jats:italic>F. prausnitzii</jats:italic>. 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. |
| first_indexed | 2024-09-23T08:40:43Z |
| format | Article |
| id | mit-1721.1/154888 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:17:17Z |
| publishDate | 2024 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1548882024-12-23T06:11:55Z An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii Zhang, Jianbo Huang, Yu-Ja Trapecar, Martin Wright, Charles Schneider, Kirsten Kemmitt, John Hernandez-Gordillo, Victor Yoon, Jun Young Poyet, Mathilde Alm, Eric J. Breault, David T. Trumper, David L. Griffith, Linda G. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Center for Gynepathology Research 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 <jats:italic>Faecalibacterium prausnitzii/Faecalibacterium duncaniae</jats:italic> with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4<jats:sup>+</jats:sup> 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 <jats:italic>F. prausnitzii</jats:italic> (GuMI-APC-FP), <jats:italic>F. prausnitzii</jats:italic> increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (<jats:italic>TLR1</jats:italic>) and interferon alpha 1 (<jats:italic>IFNA1</jats:italic>) 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<jats:sup>+</jats:sup> naive T cells (GuMI-APCT-FP), <jats:italic>TLR1</jats:italic>, <jats:italic>IFNA1</jats:italic>, and <jats:italic>IDO1</jats:italic> transcription levels decreased with a simultaneous increase in <jats:italic>F. prausnitzii</jats:italic>-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 <jats:italic>F. prausnitzii</jats:italic>. 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. 2024-05-09T18:49:59Z 2024-05-09T18:49:59Z 2024-03-29 2024-05-09T18:45:47Z Article http://purl.org/eprint/type/JournalArticle 2055-5008 https://hdl.handle.net/1721.1/154888 Zhang, J., Huang, YJ., Trapecar, M. et al. An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii. npj Biofilms Microbiomes 10, 31 (2024) en 10.1038/s41522-024-00501-z npj Biofilms and Microbiomes Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Springer Science and Business Media LLC |
| spellingShingle | Zhang, Jianbo Huang, Yu-Ja Trapecar, Martin Wright, Charles Schneider, Kirsten Kemmitt, John Hernandez-Gordillo, Victor Yoon, Jun Young Poyet, Mathilde Alm, Eric J. Breault, David T. Trumper, David L. Griffith, Linda G. An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii |
| title | An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii |
| title_full | An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii |
| title_fullStr | An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii |
| title_full_unstemmed | An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii |
| title_short | An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii |
| title_sort | immune competent human gut microphysiological system enables inflammation modulation by faecalibacterium prausnitzii |
| url | https://hdl.handle.net/1721.1/154888 |
| work_keys_str_mv | AT zhangjianbo animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT huangyuja animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT trapecarmartin animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT wrightcharles animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT schneiderkirsten animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT kemmittjohn animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT hernandezgordillovictor animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT yoonjunyoung animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT poyetmathilde animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT almericj animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT breaultdavidt animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT trumperdavidl animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT griffithlindag animmunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT zhangjianbo immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT huangyuja immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT trapecarmartin immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT wrightcharles immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT schneiderkirsten immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT kemmittjohn immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT hernandezgordillovictor immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT yoonjunyoung immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT poyetmathilde immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT almericj immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT breaultdavidt immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT trumperdavidl immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii AT griffithlindag immunecompetenthumangutmicrophysiologicalsystemenablesinflammationmodulationbyfaecalibacteriumprausnitzii |