A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth
We establish a murine lung-on-chip infection model and use time-lapse imaging to reveal the dynamics of host-Mycobacterium tuberculosis interactions at an air-liquid interface with a spatiotemporal resolution unattainable in animal models and to probe the direct role of pulmonary surfactant in early...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/59961 |
| _version_ | 1828376275011502080 |
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| author | Vivek V Thacker Neeraj Dhar Kunal Sharma Riccardo Barrile Katia Karalis John D McKinney |
| author_facet | Vivek V Thacker Neeraj Dhar Kunal Sharma Riccardo Barrile Katia Karalis John D McKinney |
| author_sort | Vivek V Thacker |
| collection | DOAJ |
| description | We establish a murine lung-on-chip infection model and use time-lapse imaging to reveal the dynamics of host-Mycobacterium tuberculosis interactions at an air-liquid interface with a spatiotemporal resolution unattainable in animal models and to probe the direct role of pulmonary surfactant in early infection. Surfactant deficiency results in rapid and uncontrolled bacterial growth in both macrophages and alveolar epithelial cells. In contrast, under normal surfactant levels, a significant fraction of intracellular bacteria are non-growing. The surfactant-deficient phenotype is rescued by exogenous addition of surfactant replacement formulations, which have no effect on bacterial viability in the absence of host cells. Surfactant partially removes virulence-associated lipids and proteins from the bacterial cell surface. Consistent with this mechanism, the attenuation of bacteria lacking the ESX-1 secretion system is independent of surfactant levels. These findings may partly explain why smokers and elderly persons with compromised surfactant function are at increased risk of developing active tuberculosis. |
| first_indexed | 2024-04-14T07:58:41Z |
| format | Article |
| id | doaj.art-a70932b797244b27ab0d6dcfe4d8ec7e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:58:41Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a70932b797244b27ab0d6dcfe4d8ec7e2022-12-22T02:04:58ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.59961A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growthVivek V Thacker0https://orcid.org/0000-0002-1681-627XNeeraj Dhar1https://orcid.org/0000-0002-5887-8137Kunal Sharma2https://orcid.org/0000-0001-8086-3436Riccardo Barrile3https://orcid.org/0000-0002-7301-3959Katia Karalis4John D McKinney5https://orcid.org/0000-0002-0557-3479School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandSchool of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandSchool of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandEmulate Inc, Boston, United StatesEmulate Inc, Boston, United StatesSchool of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, SwitzerlandWe establish a murine lung-on-chip infection model and use time-lapse imaging to reveal the dynamics of host-Mycobacterium tuberculosis interactions at an air-liquid interface with a spatiotemporal resolution unattainable in animal models and to probe the direct role of pulmonary surfactant in early infection. Surfactant deficiency results in rapid and uncontrolled bacterial growth in both macrophages and alveolar epithelial cells. In contrast, under normal surfactant levels, a significant fraction of intracellular bacteria are non-growing. The surfactant-deficient phenotype is rescued by exogenous addition of surfactant replacement formulations, which have no effect on bacterial viability in the absence of host cells. Surfactant partially removes virulence-associated lipids and proteins from the bacterial cell surface. Consistent with this mechanism, the attenuation of bacteria lacking the ESX-1 secretion system is independent of surfactant levels. These findings may partly explain why smokers and elderly persons with compromised surfactant function are at increased risk of developing active tuberculosis.https://elifesciences.org/articles/59961organ-on-chipMycobacterium tuberculosishost-pathogen interactionstime-lapse microscopypulmonary surfactantdisease models |
| spellingShingle | Vivek V Thacker Neeraj Dhar Kunal Sharma Riccardo Barrile Katia Karalis John D McKinney A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth eLife organ-on-chip Mycobacterium tuberculosis host-pathogen interactions time-lapse microscopy pulmonary surfactant disease models |
| title | A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth |
| title_full | A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth |
| title_fullStr | A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth |
| title_full_unstemmed | A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth |
| title_short | A lung-on-chip model of early Mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth |
| title_sort | lung on chip model of early mycobacterium tuberculosis infection reveals an essential role for alveolar epithelial cells in controlling bacterial growth |
| topic | organ-on-chip Mycobacterium tuberculosis host-pathogen interactions time-lapse microscopy pulmonary surfactant disease models |
| url | https://elifesciences.org/articles/59961 |
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