The Cytosolic Bacterial Peptidoglycan Sensor Nod2 Affords Stem Cell Protection and Links Microbes to Gut Epithelial Regeneration
| Autor: | Philippe Jay, Philippe J. Sansonetti, Giulia Nigro, Raffaella Rossi, Pierre-Henri Commere |
|---|---|
| Přispěvatelé: | Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagopole (CITECH), Institut Pasteur [Paris] (IP), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This work was supported by European Research Council (ERC) advanced grant HOMEOEPITH to P.J.S., who is also a Howard Hughes Medical Institute senior foreign scholar. G.N. and R.R. were supported by ERC grant HOMEOEPITH. We thank J.-P. Hugot and I. Boneca for providing the transgenic Nod2 KO and Nod1 KO mice, D. Mengin-Lecreulx for providing Tetra-dap, and Ellen T. Arena and Pamela Schnupf for critical reading and proofreading of the manuscript. We gratefully acknowledge Thierry Pedron for helpful discussions and technical support., We acknowledge the PFID and PFC at the Imagopole of Institut Pasteur for their precious help with imaging and sorting and the DIM-STEM-Pôle Ile-de-France 'cellules souches et médecine' for funding the Moflo Astrios., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Chaire Microbiologie et Maladies infectieuses, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2014 |
| Předmět: |
MESH: Intestines/microbiology
Cancer Research Cell type MESH: Gastrointestinal Tract/drug effects [SDV]Life Sciences [q-bio] Crypt MESH: Acetylmuramyl-Alanyl-Isoglutamine/pharmacology MESH: Organoids Biology MESH: Mice Knockout digestive system Microbiology chemistry.chemical_compound MESH: Gastrointestinal Tract/microbiology MESH: Receptors G-Protein-Coupled/metabolism MESH: Mice Inbred C57BL Immunology and Microbiology(all) Virology MESH: Receptors G-Protein-Coupled/genetics MESH: Intestines/physiology Organoid MESH: Epithelium/microbiology Molecular Biology Innate immune system MESH: AnimalsAnimals MESH: Regeneration LGR5 MESH: Gastrointestinal Tract/cytology MESH: Stem Cells/drug effects MESH: Intestines/cytology MESH: Cytosol/metabolism [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Cytoprotection digestive system diseases Cell biology MESH: Cytoprotection chemistry MESH: Acetylmuramyl-Alanyl-Isoglutamine/chemistry Parasitology Peptidoglycan Stem cell MESH: Peptidoglycan/chemistry MESH: Epithelium/drug effects MESH: Nod2 Signaling Adaptor Protein/metabolism |
| Zdroj: | Cell Host and Microbe Cell Host and Microbe, 2014, 15 (6), pp.792--798. ⟨10.1016/j.chom.2014.05.003⟩ Cell Host and Microbe, Elsevier, 2014, 15 (6), pp.792--798. ⟨10.1016/j.chom.2014.05.003⟩ |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2014.05.003 |
| Popis: | Comment in : Nod-like receptors have a grip on stem cells. [Cell Host Microbe. 2014]; International audience; The intestinal crypt is a site of potential interactions between microbiota products, stem cells, and other cell types found in this niche, including Paneth cells, and thus offers a potential for commensal microbes to influence the host epithelium. However, the complexity of this microenvironment has been a challenge to deciphering the underlying mechanisms. We used in vitro cultured organoids of intestinal crypts from mice, reinforced with in vivo experiments, to examine the crypt-microbiota interface. We find that within the intestinal crypt, Lgr5(+) stem cells constitutively express the cytosolic innate immune sensor Nod2 at levels much higher than in Paneth cells. Nod2 stimulation by its bona fide agonist, muramyl-dipeptide (MDP), a peptidoglycan motif common to all bacteria, triggers stem cell survival, which leads to a strong cytoprotection against oxidative stress-mediated cell death. Thus, gut epithelial restitution is Nod2 dependent and triggered by the presence of microbiota-derived molecules. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|