Fig. 2. Activation and Signaling pathways of NOD2MDP-dependent: NOD2 detects MDP from inside and outside the bacteria. PHT1, an endosomal peptide transporter protein of the SLC15 family, is transported into the cytosol by host cells following phagocytosis of bacteria and subsequent bacterial degradation. The plasma membrane transport hPepT1 directly transports peptidoglycan into the cytoplasm. MDP-independent: the involvement of NOD2 in viral ssRNA recognition followed by interaction with MAVS induces IRF3 activation and triggers IFN-β gene expression. ER stress recruits TRAF2 and enables NOD2 activation in response to unfolded proteins. Alterations in the cytoskeleton can also stimulate NOD2. NOD2 activation followed by CARD-CARD oligomerization induces RIP2 activation and activates NF-κB and MAPKs, which are responsible for triggering the expression of inflammatory cytokines. NOD2-mediated autophagy is essential for the control of bacterial.