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 language | English |
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Pages (from-to) | 706-713 |
Number of pages | 8 |
Journal | Infection and Immunity |
Volume | 75 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Feb 2007 |
Externally published | Yes |
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