The innate immune system, that mediates the first line of defense against microbial pathogens, is essential for the activation of acquired immune system.

Mutations in Nod2, one of the innate immune factors, have been associated with Crohn's disease, the inflammatory bowel disease, and Blau syndrome, characterized by systemic granuloma. Our analysis revealed that the Nod2 variants carried by CD patients demonstrated impaired MDP-dependent response, and Nod2 alleles associated with Blau's syndrome promoted MDP-independent activation. We also identified precise ligand recognition mechanism through the analysis of 500 Nod2 mutants.