The Cytosolic Bacterial Peptidoglycan Sensor Nod2 Affords Stem Cell Protection and Links Microbes to Gut Epithelial Regeneration

摘要: The intestinal crypt is a site of potential interactions between microbiota products, stem cells, and other cell types found in this niche, including Paneth thus offers for commensal microbes to influence the host epithelium. However, complexity microenvironment has been challenge deciphering underlying mechanisms. We used vitro cultured organoids crypts from mice, reinforced with vivo experiments, examine crypt-microbiota interface. find that within crypt, Lgr5(+) cells constitutively express cytosolic innate immune sensor Nod2 at levels much higher than cells. stimulation by its bona fide agonist, muramyl-dipeptide (MDP), peptidoglycan motif common all bacteria, triggers survival, which leads strong cytoprotection against oxidative stress-mediated death. Thus, gut epithelial restitution dependent triggered presence microbiota-derived molecules.