Fig. 5.

Nod2 is the intracellular receptor for recognition of SCW fragments. (A and B) HEK-293 cells cotransfected with either Nod1 or Nod2 expressing plasmid and an NF-κB-reporter construct. Cells were exposed to a dose range of SCW fragments and positive controls (FK156, MDP). (C) Peritoneal macrophages were stimulated with 1 μg/ml SCW for 24 h; thereafter, TNF was determined by Luminex assay. (D) Schematic representation of the putative Nod1-Nod2 protein complex controlling TLR2 driven pathway. SCW fragments trigger TLR2 pathway directly and after release of MDP from the SCW peptidoglycans, the Nod2 cascade is activated. Enhanced cytokine production will occur by simultaneous activation of TLR2 and Nod2 pathways. Nod1-Nod2 complexes interfere with the latter pathways by inactivation Nod2 receptor.