Recent evidence suggests that the nucleotide-binding oligomerization domain protein 1 (NOD1) has an important role in bacterial recognition and may function as a specific host pattern recognition receptor (PRR) in intracellular compartments. In the June 8 advanced online publication of Nature Immunology, Mathias Chamaillard and colleagues at the University of Michigan Medical School, confirm NOD1 as essential in host recognition of bacterial peptidoglycan containing diaminopimelic acid (Nature Immunology, DOI:10.1038/ni945, June 8, 2003).

Chamaillard et al. performed biochemical and functional analyses using highly purified and synthetic bacterial cell wall peptidoglycan (PGN) compounds. They observed that the core structure recognized by NOD1 is a dipeptide, γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP)—known to exist only in limited number of bacteria (Escherichia coli and several gram-positive bacteria, such as Bacillus subtilis and Listeria monocytogenes). In addition, they showed that murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response.

"These results indicate that NOD1 acts as an intracellular PRR for a subset of bacteria through the detection of iE-DAP. However, further studies with mutant mice are needed to understand the biological function of NOD1. Bacteria carrying DAP-containing PGN also possess molecules capable of stimulating multiple PRRs. Thus, analysis of NOD1 function in the absence and presence of other PRRs may be needed to unravel the role of NOD1 in host defense against bacteria," conclude the authors.