Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i>
Infections by the zoonotic foodborne bacterium <i>Campylobacter jejuni</i> (<i>C. jejuni</i>) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation,...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8872 |
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| author | Fábia D. Lobo de Sá Steffen Backert Praveen K. Nattramilarasu Soraya Mousavi Geoffrey I. Sandle Stefan Bereswill Markus M. Heimesaat Jörg-Dieter Schulzke Roland Bücker |
| author_facet | Fábia D. Lobo de Sá Steffen Backert Praveen K. Nattramilarasu Soraya Mousavi Geoffrey I. Sandle Stefan Bereswill Markus M. Heimesaat Jörg-Dieter Schulzke Roland Bücker |
| author_sort | Fábia D. Lobo de Sá |
| collection | DOAJ |
| description | Infections by the zoonotic foodborne bacterium <i>Campylobacter jejuni</i> (<i>C. jejuni</i>) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during <i>C. jejuni</i> infection, using intestinal epithelial cells and mouse models focused on the interaction of <i>C. jejuni</i> with the VD signaling pathway and VD treatment to improve <i>C. jejuni</i>-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in <i>C. jejuni</i>-infected epithelial cells and IL-10<sup>−/−</sup> mice. Furthermore, interference of <i>C. jejuni</i> with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for <i>C. jejuni</i> treatment in humans and animals. |
| first_indexed | 2024-03-10T08:43:36Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:43:36Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-183a0699158346e5bfa3192137b0c1682023-11-22T08:01:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216887210.3390/ijms22168872Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i>Fábia D. Lobo de Sá0Steffen Backert1Praveen K. Nattramilarasu2Soraya Mousavi3Geoffrey I. Sandle4Stefan Bereswill5Markus M. Heimesaat6Jörg-Dieter Schulzke7Roland Bücker8Nutritional Medicine/Clinical Physiology, Medical Department, Division of Gastroenterology, Infectious Diseases, Rheumatology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyDivision of Microbiology, Department of Biology, University of Erlangen-Nürnberg, 91058 Erlangen, GermanyNutritional Medicine/Clinical Physiology, Medical Department, Division of Gastroenterology, Infectious Diseases, Rheumatology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyInstitute of Medical Research at St James’s, St James’s University Hospital, Leeds LS9 7TF, UKInstitute of Microbiology, Infectious Diseases and Immunology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyInstitute of Microbiology, Infectious Diseases and Immunology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyNutritional Medicine/Clinical Physiology, Medical Department, Division of Gastroenterology, Infectious Diseases, Rheumatology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyNutritional Medicine/Clinical Physiology, Medical Department, Division of Gastroenterology, Infectious Diseases, Rheumatology, Charité—Universitätsmedizin Berlin, 12203 Berlin, GermanyInfections by the zoonotic foodborne bacterium <i>Campylobacter jejuni</i> (<i>C. jejuni</i>) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during <i>C. jejuni</i> infection, using intestinal epithelial cells and mouse models focused on the interaction of <i>C. jejuni</i> with the VD signaling pathway and VD treatment to improve <i>C. jejuni</i>-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in <i>C. jejuni</i>-infected epithelial cells and IL-10<sup>−/−</sup> mice. Furthermore, interference of <i>C. jejuni</i> with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for <i>C. jejuni</i> treatment in humans and animals.https://www.mdpi.com/1422-0067/22/16/8872tight junctioncampylobacteriosisapoptosistranslocationleaky gutvitamin D receptor signaling pathway |
| spellingShingle | Fábia D. Lobo de Sá Steffen Backert Praveen K. Nattramilarasu Soraya Mousavi Geoffrey I. Sandle Stefan Bereswill Markus M. Heimesaat Jörg-Dieter Schulzke Roland Bücker Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i> International Journal of Molecular Sciences tight junction campylobacteriosis apoptosis translocation leaky gut vitamin D receptor signaling pathway |
| title | Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i> |
| title_full | Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i> |
| title_fullStr | Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i> |
| title_full_unstemmed | Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i> |
| title_short | Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by <i>Campylobacter jejuni</i> |
| title_sort | vitamin d reverses disruption of gut epithelial barrier function caused by i campylobacter jejuni i |
| topic | tight junction campylobacteriosis apoptosis translocation leaky gut vitamin D receptor signaling pathway |
| url | https://www.mdpi.com/1422-0067/22/16/8872 |
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