Chapter 32 - NOD receptor recognition of peptidoglycan

Abstract

Peptidoglycan (PG) is a major and almost ubiquitous component of the bacterial cell wall. It has been known since the 1970s to have potent biological activity on higher eukaryotes. The molecular basis of this potent activity was elucidated recently with the discovery of a new family of intracellular receptors of the innate immune system, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs). Nod1 and Nod2 became the archetype of a new family of intracellular innate immune receptors termed NLRs. These are modular proteins with, in general, an N-terminal effector domain, a central nucleotide-binding site (NBS or NATCH domain) and a ligand-sensing C-terminal domain of leucine-rich repeats (LRRs) similar to TLRs. Nod1 and Nod2 have been shown to sense different muropeptides structures. Thus, Nod1 senses specifically meso-diaminopimelic-type muropeptides originating from mostly Gram-negative bacteria, whereas Nod2 is a more general sensor of muropeptides. The discovery of the Nod-like receptors (NLRs) opened a new field of research on host–microbe interactions in which NLRs work in parallel and/or with Toll-like receptors to sense bacteria. Of note, NLRs have been shown to fulfill important roles in detecting pathogens such as Helicobacter pylori, Listeria monocytogenes or Shigella flexneri. In exchange, bacteria have evolved diverse strategies to modulate the host response by modifying their peptidoglycan or the amount of muropeptide shed.