Jana Meiners, Vittoria Palmieri, Robert Klopfleisch, Jana-Fabienne Ebel, Lukasz Japtok, Fabian Schumacher, Ayan Mohamud Yusuf, Katrin Anne Becker, Julia Zöller, Matthias Hose, Burkhard Kleuser, Dirk Matthias Hermann, Richard N. Kolesnick, Jan Buer, Wiebke Hansen, Astrid M. Westendorf
- 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 T(h)1 and T(h)17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice.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 T(h)1 and T(h)17 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.…
MetadatenAuthor details: | Jana MeinersGND, Vittoria Palmieri, Robert KlopfleischORCiDGND, Jana-Fabienne Ebel, Lukasz JaptokGND, Fabian SchumacherORCiDGND, Ayan Mohamud YusufGND, Katrin Anne BeckerORCiDGND, Julia ZöllerGND, Matthias HoseGND, Burkhard KleuserORCiDGND, Dirk Matthias HermannGND, Richard N. Kolesnick, Jan BuerGND, Wiebke HansenGND, Astrid M. WestendorfGND |
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DOI: | https://doi.org/10.3389/fimmu.2019.01386 |
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ISSN: | 1664-3224 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31275322 |
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Title of parent work (English): | Frontiers in immunology |
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Publisher: | Frontiers Research Foundation |
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Place of publishing: | Lausanne |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2019/06/19 |
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Publication year: | 2019 |
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Release date: | 2021/01/20 |
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Tag: | Citrobacter rodentium; T(h)1; T(h)17; acid sphingomyelinase; amitriptyline; colitis |
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Volume: | 10 |
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Number of pages: | 14 |
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Funding institution: | Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG-GRK2098, GRK1949] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Publishing method: | Open Access / Gold Open-Access |
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| DOAJ gelistet |
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License (German): | CC-BY - Namensnennung 4.0 International |
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