Modification of the structure of peptidoglycan is a strategy to avoid detection by nucleotide-binding oligomerization domain protein 1

Margreet A. Wolfert, Abhijit Roychowdhury, Geert-Jan Boons

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Nucleotide-binding oligomerization domain (NOD) protein 1 (NOD1) and NOD2 are pathogen recognition receptors that sense breakdown products of peptidoglycan (PGN) (muropeptides). It is shown that a number of these muropeptides can induce tumor necrosis factor alpha (TNF-α) gene expression without significant TNF-α translation. This translation block is lifted when the muropeptides are coincubated with lipopolysaccharide (LPS), thereby accounting for an apparently synergistic effect of the muropeptides with LPS on TNF-α protein production. The compounds that induced synergistic effects were also able to activate NF-κB in a NOD1- or NOD2-dependent manner, implicating these proteins in synergistic TNF-α secretion. It was found that a diaminopimelic acid (DAP)-containing muramyl tetrapeptide could activate NF-κB in a NOD1-dependent manner, demonstrating that an exposed DAP is not essential for NOD1 sensing. The activity was lost when the α-carboxylic acid of iso-glutamic acid was modified as an amide. However, agonists of NOD2, such as muramyl dipeptide and lysine-containing muramyl tripeptides, were not affected by amidation of the α-carboxylic acid of iso-glutamic acid. Many pathogens modify the α-carboxylic acid of iso-glutamic acid of PGN, and thus it appears this is a strategy to avoid recognition by the host innate immune system. This type of immune evasion is in particular relevant for NOD1. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)706-713
Number of pages8
JournalInfection and Immunity
Volume75
Issue number2
DOIs
Publication statusPublished - 1 Feb 2007
Externally publishedYes

Keywords

  • carboxyl group
  • caspase recruitment domain protein 15
  • caspase recruitment domain protein 4
  • diaminopimelic acid
  • glutamic acid
  • immunoglobulin enhancer binding protein
  • lipopolysaccharide
  • muramyl dipeptide
  • muramyl tripeptide
  • peptidoglycan
  • tumor necrosis factor
  • unclassified drug
  • amidation
  • antigen recognition
  • article
  • controlled study
  • cytokine production
  • cytokine release
  • gene expression
  • human
  • human cell
  • innate immunity
  • nonhuman
  • priority journal
  • protein structure
  • RNA translation

Fingerprint

Dive into the research topics of 'Modification of the structure of peptidoglycan is a strategy to avoid detection by nucleotide-binding oligomerization domain protein 1'. Together they form a unique fingerprint.

Cite this