An Essential Role for NOD1 in Host Recognition of Bacterial Peptidoglycan Containing Diaminopimelic Acid

Nat Immunol. 2003 Jul;4(7):702-7. doi: 10.1038/ni945. Epub 2003 Jun 6.

Abstract

Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Bacterial Infections / immunology*
  • Carrier Proteins / physiology*
  • Cell Line
  • Cytokines / biosynthesis
  • Diaminopimelic Acid / metabolism*
  • Female
  • Humans
  • Immunity, Innate / physiology*
  • Intracellular Signaling Peptides and Proteins*
  • Lipopolysaccharides / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Peptidoglycan / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • NOD1 protein, human
  • NOD2 protein, human
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Peptidoglycan
  • Diaminopimelic Acid