The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration

Cell Host Microbe. 2014 Jun 11;15(6):792-8. doi: 10.1016/j.chom.2014.05.003. Epub 2014 May 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / chemistry
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology*
  • Animals
  • Cytoprotection
  • Cytosol / metabolism
  • Epithelium / drug effects
  • Epithelium / microbiology
  • Gastrointestinal Tract / cytology
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / microbiology*
  • Intestines / cytology
  • Intestines / microbiology
  • Intestines / physiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Organoids
  • Peptidoglycan / chemistry
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Regeneration
  • Stem Cells / drug effects


  • Lgr5 protein, mouse
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse
  • Peptidoglycan
  • Receptors, G-Protein-Coupled
  • Acetylmuramyl-Alanyl-Isoglutamine