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The Cytosolic Bacterial Peptidoglycan Sensor Nod2 Affords Stem Cell Protection and Links Microbes to Gut Epithelial Regeneration
Cell Host & Microbe, Issue: 6, Volume: 15, Pages: 792-798. | 2014-01-06
0 Patent citations    64 Scholarly citations     Reference Count: 24
Giulia Nigro;Raffaella Rossi;Pierre-Henri Commere;Philippe Jay;Philippe J Sansonetti

摘要

Summary 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.


机构

Pasteur Institute;Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, 75015 Paris, France; INSERM U 786, Institut Pasteur, 75015 Paris, France.Pasteur Institute;Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, 75015 Paris, France; Institut de Génomique Fonctionnelle, CNRS UMR 5203, Inserm U661, 34000 Montpellier, France.Pasteur Institute;Institut Pasteur, Imagopole, 75015 Paris, France.French Institute of Health and Medical Research;Institut de Génomique Fonctionnelle, CNRS UMR 5203, Inserm U661, 34000 Montpellier, France.Pasteur Institute;Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, 75015 Paris, France; INSERM U 786, Institut Pasteur, 75015 Paris, France; Chaire de Microbiologie et Maladies Infectieuses, Collège de France, 75005 Paris, France. Electronic address: philippe.sansonetti@pasteur.fr.


文献类型:

journal article;research support, non-u.s. gov't;

出版商:

Cell Press

发表时间:

2014-01-06

基金信息

Howard Hughes Medical Institute()United States