Detection of enteric pathogens by the nodosome

• NOD1 and NOD2 monitor the integrity of the cytosol to detect danger signals.
• Excessive activation of small Rho GTPases is a danger signal detected by NOD1.
• NOD1 detects virulence factors of enteric pathogens that activate small Rho GTPases.
• Excessive activation of small Rho GTPases is a danger signal in insects and mammals.

Nucleotide-binding oligomerization domain protein (NOD)1 and NOD2 participate in signaling pathways that detect pathogen-induced processes, such as the presence of peptidoglycan fragments in the host cell cytosol, as danger signals. Recent work suggests that peptidoglycan fragments activate NOD1 indirectly, through activation of the small Rho GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1). Excessive activation of small Rho GTPases by virulence factors of enteric pathogens also triggers the NOD1 signaling pathway. Many enteric pathogens use virulence factors that alter the activation state of small Rho GTPases, thereby manipulating the host cell cytoskeleton of intestinal epithelial cells to promote bacterial attachment or entry. These data suggest that the NOD1 signaling pathway in intestinal epithelial cells provides an important sentinel function for detecting ‘breaking and entering’ by enteric pathogens.