Nucleotide oligomerization binding domain-like receptor signaling enhances dendritic cell-mediated cross-priming in vivo

Nucleotide oligomerization binding domain (Nod)-like receptors are critical cytosolic sensors for the recognition of bacterial peptidoglycan. However, their role in the induction of dendritic cell (DC)-mediated cross-priming remains unclear. In this study, we demonstrate that injecting ligands for Nod1 and Nod2 along with Ag into wild-type mice significantly enhanced the cross-priming of Agspecific CD8⁺ T cells by CD8α⁺ DCs, as assessed from the expansion of IFN-γ⁺ CD8⁺ T cells, CTL activity against Ag-pulsed targets, and the rejection of transplanted tumors expressing the cognate Ag. The enhancement of CD8α⁺ DC-mediated cross-priming was likely due to the upregulation of Ag cross-presentation and of costimulatory molecules. Our findings collectively indicate that Nod1/2 signaling is critical for the optimal induction of DC cross-priming in vivo, which may offer an alternative therapeutic pathway in cancer and hosts refractory to TLR signals or paralyzed by viral evasion strategy.