The role of altered microbial signaling via mutant NODs in intestinal inflammation

Recently, a new class of intracellular pattern recognition receptors belonging to the family of nucleotide binding and oligomerization domain (NOD)-like receptors that includes NOD1, NOD2 and IPAF has been described. These proteins are involved in recognizing bacterial components or their degradation constituents that are delivered within the cytoplasm. In this review we will analyze the role of NOD proteins in regulating immune homeostasis.

After an initial description of advances in our understanding of the function of these proteins, this review will focus on the contradictory finding that even though mutations in NOD2 proteins lead to a loss of function phenotype, the outcome is an increased inflammatory response. Different hypotheses to reconcile this observation will be proposed.

The cellular and tissue distribution of NOD molecules as well as their role in regulating inflammatory cytokine release renders these proteins particularly important in controlling the development of inflammatory reactions. This is confirmed by the discovery that mutations in the genes that code for NOD1 and NOD2 confer increased susceptibility to inflammatory bowel disease. We will discuss NOD2 involvement in the development of Crohn's disease.