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Sphingosine kinase 1/S1P receptor signaling axis is essential for cellular uptake of Neisseria meningitidis in brain endothelial cells.
| العنوان: | Sphingosine kinase 1/S1P receptor signaling axis is essential for cellular uptake of Neisseria meningitidis in brain endothelial cells. |
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| المؤلفون: | Ingo Fohmann, Alina Weinmann, Fabian Schumacher, Simon Peters, Agata Prell, Cynthia Weigel, Sarah Spiegel, Burkhard Kleuser, Alexandra Schubert-Unkmeir |
| المصدر: | PLoS Pathogens, Vol 19, Iss 11, p e1011842 (2023) |
| بيانات النشر: | Public Library of Science (PLoS), 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | Invasion of brain endothelial cells (BECs) is central to the pathogenicity of Neisseria meningitidis infection. Here, we established a key role for the bioactive sphingolipid sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) 2 in the uptake process. Quantitative sphingolipidome analyses of BECs infected with N. meningitidis revealed elevated S1P levels, which could be attributed to enhanced expression of the enzyme sphingosine kinase 1 and its activity. Increased activity was dependent on the interaction of meningococcal type IV pilus with the endothelial receptor CD147. Concurrently, infection led to increased expression of the S1PR2. Blocking S1PR2 signaling impaired epidermal growth factor receptor (EGFR) phosphorylation, which has been shown to be involved in cytoskeletal remodeling and bacterial endocytosis. Strikingly, targeting S1PR1 or S1PR3 also interfered with bacterial uptake. Collectively, our data support a critical role of the SphK/S1P/S1PR axis in the invasion of N. meningitidis into BECs, defining a potential target for adjuvant therapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011842&type=printable; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1011842&type=printable |
| DOI: | 10.1371/journal.ppat.1011842 |
| URL الوصول: | https://doaj.org/article/c31e77c4fec344e8933a84ec410cf0cc |
| رقم الانضمام: | edsdoj.31e77c4fec344e8933a84ec410cf0cc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1011842&type=printable |