Giving a Nod2 the Right Target

© 2003 Nature Publishing Group

Phagocytosed microorganisms release ligands recognized by NOD proteins and peptides that associate with MHC II molecules. Recognition of intracellular ligands by NOD proteins and extracellular ligands by Toll-like receptors mediates the activation of signaling pathways including those downstream of NF-κB like cytokine secretion, and co-stimulatory receptor expression (e.g. CD80 and CD86). (From N. Inohara, G. Nuñez, Nat Rev Immunol, 3:371–82, 2003.)

Nod1 and Nod2 are no strangers to Hot Papers. Nor is Gabriel Nuñez, the University of Michigan pathologist whose back-to-back discoveries concerning the cytosolic proteins were featured last year. The 2001 papers by Nuñez and colleagues demonstrated Nod1 and Nod2 (also referred to as CARD15 and CARD4, respectively) sense intracellular pathogens and activate NF-κB, a transcription factor central to immunoregulation and inflammation, and that mutations in the Nod2 gene were a risk factor for Crohn disease.1 At the time, there was some controversy as ...