In light of recent data showing the role of Nod2 in inducing tolerance to bacterial ligands in vitro and the data in this report showing the in vivo results of Nod2 deficiency in a slowly progressing arthritis, we believe that a model of differing roles of Nod2 in early and prolonged infection is a likely mechanism to reconcile opposing studies on the role of Nod2 in inflammatory responses. The gene discussed is NOD2; the disease is arthritic joint disease.