Academic Journal
Mycobacterium leprae Phenolglycolipid-1 Expressed by Engineered M. bovis BCG Modulates Early Interaction with Human Phagocytes
| العنوان: | Mycobacterium leprae Phenolglycolipid-1 Expressed by Engineered M. bovis BCG Modulates Early Interaction with Human Phagocytes |
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| المؤلفون: | Tabouret, Guillaume, Astarie-Dequeker, Catherine, Demangel, Caroline, Malaga, Wladimir, Constant, Patricia, Ray, Aurélie, Honoré, Nadine, Bello, Nana Fatimath, Perez, Esther, Daffé, Mamadou, Guilhot, Christophe |
| المساهمون: | Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Pathogénomique mycobactérienne intégrée, Institut Pasteur Paris (IP), This work was funded by the Centre National de la Recherche Scientifique (CNRS), and the Agence Nationale de la Recherche grant 06-MIME-032-02. The NMR spectrometers were financed by the CNRS, the University Paul Sabatier, the Région Midi-Pyrénées and the European Structural Funds (FEDER)., ANR-06-MIME-0032,PGLEP,Le rôle du phénol-glycolipide 1 du bacille lépreux dans l'invasion cellulaire, la neuropathie et l'immunosuppression(2006) |
| المصدر: | ISSN: 1553-7366. |
| بيانات النشر: | HAL CCSD Public Library of Science |
| سنة النشر: | 2010 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | PHENOLIC GLYCOLIPID-1, PHTHIOCEROL DIESTER, HUMAN MONOCYTES, BIOSYNTHESIS, CD11B/CD18, ACTIVATION, TUBERCULOSIS COMPLEX, VIRULENCE FACTORS, DENDRITIC CELLS, RECEPTORS, MESH: Animals, MESH: Antigen Presentation/genetics, MESH: Glycolipids/genetics, MESH: Glycolipids/metabolism, MESH: Glycolipids/physiology, MESH: Humans, MESH: Immune Evasion/genetics, MESH: Immune Evasion/immunology, MESH: Immunity, Innate/genetics, Innate/physiology, MESH: Models, Biological, MESH: Mycobacterium bovis/genetics, MESH: Antigen Presentation/physiology, MESH: Mycobacterium bovis/metabolism, MESH: Mycobacterium leprae/genetics, MESH: Phagocytes/immunology, MESH: Phagocytes/metabolism, MESH: Protein Engineering/methods |
| الوصف: | International audience ; The species-specific phenolic glycolipid 1 (PGL-1) is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3) for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/20975946; pasteur-01376090; https://pasteur.hal.science/pasteur-01376090; https://pasteur.hal.science/pasteur-01376090/document; https://pasteur.hal.science/pasteur-01376090/file/journal.ppat.1001159.PDF; PRODINRA: 260125; PUBMED: 20975946; WOS: 000283652200032 |
| DOI: | 10.1371/journal.ppat.1001159 |
| الاتاحة: | https://pasteur.hal.science/pasteur-01376090 https://pasteur.hal.science/pasteur-01376090/document https://pasteur.hal.science/pasteur-01376090/file/journal.ppat.1001159.PDF https://doi.org/10.1371/journal.ppat.1001159 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.8D5A2FD3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.ppat.1001159 |
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