Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis
Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present stud...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01386/full |
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| author | Jana Meiners Vittoria Palmieri Robert Klopfleisch Jana-Fabienne Ebel Lukasz Japtok Fabian Schumacher Fabian Schumacher Ayan Mohamud Yusuf Katrin A. Becker Julia Zöller Matthias Hose Burkhard Kleuser Dirk M. Hermann Richard N. Kolesnick Jan Buer Wiebke Hansen Astrid M. Westendorf |
| author_facet | Jana Meiners Vittoria Palmieri Robert Klopfleisch Jana-Fabienne Ebel Lukasz Japtok Fabian Schumacher Fabian Schumacher Ayan Mohamud Yusuf Katrin A. Becker Julia Zöller Matthias Hose Burkhard Kleuser Dirk M. Hermann Richard N. Kolesnick Jan Buer Wiebke Hansen Astrid M. Westendorf |
| author_sort | Jana Meiners |
| collection | DOAJ |
| description | Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of Citrobacter (C.) rodentium-driven colitis. C. rodentium is an enteric pathogen and induces colonic inflammation very similar to the pathology in patients with ulcerative colitis. We found that mice with Asm deficiency or Asm inhibition were strongly susceptible to C. rodentium infection. These mice showed increased levels of C. rodentium in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory Th1 and Th17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice. These findings identified Asm as an essential regulator of mucosal immunity to the enteric pathogen C. rodentium. |
| first_indexed | 2024-12-10T08:28:45Z |
| format | Article |
| id | doaj.art-1bec017fc89c418580de39de4b07be87 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T08:28:45Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1bec017fc89c418580de39de4b07be872022-12-22T01:56:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01386458492Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven ColitisJana Meiners0Vittoria Palmieri1Robert Klopfleisch2Jana-Fabienne Ebel3Lukasz Japtok4Fabian Schumacher5Fabian Schumacher6Ayan Mohamud Yusuf7Katrin A. Becker8Julia Zöller9Matthias Hose10Burkhard Kleuser11Dirk M. Hermann12Richard N. Kolesnick13Jan Buer14Wiebke Hansen15Astrid M. Westendorf16Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Veterinary Pathology, Free University of Berlin, Berlin, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, GermanyDepartment of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, GermanyDepartment of Molecular Biology, University of Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Molecular Biology, University of Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, GermanyDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyLaboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, NY, United StatesInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of Citrobacter (C.) rodentium-driven colitis. C. rodentium is an enteric pathogen and induces colonic inflammation very similar to the pathology in patients with ulcerative colitis. We found that mice with Asm deficiency or Asm inhibition were strongly susceptible to C. rodentium infection. These mice showed increased levels of C. rodentium in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory Th1 and Th17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice. These findings identified Asm as an essential regulator of mucosal immunity to the enteric pathogen C. rodentium.https://www.frontiersin.org/article/10.3389/fimmu.2019.01386/fullCitrobacter rodentiumcolitisacid sphingomyelinaseamitriptylineTh1Th17 |
| spellingShingle | Jana Meiners Vittoria Palmieri Robert Klopfleisch Jana-Fabienne Ebel Lukasz Japtok Fabian Schumacher Fabian Schumacher Ayan Mohamud Yusuf Katrin A. Becker Julia Zöller Matthias Hose Burkhard Kleuser Dirk M. Hermann Richard N. Kolesnick Jan Buer Wiebke Hansen Astrid M. Westendorf Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis Frontiers in Immunology Citrobacter rodentium colitis acid sphingomyelinase amitriptyline Th1 Th17 |
| title | Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis |
| title_full | Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis |
| title_fullStr | Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis |
| title_full_unstemmed | Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis |
| title_short | Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis |
| title_sort | intestinal acid sphingomyelinase protects from severe pathogen driven colitis |
| topic | Citrobacter rodentium colitis acid sphingomyelinase amitriptyline Th1 Th17 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01386/full |
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