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 Ag-specific CD8(+) T cells by CD8 alpha(+) DCs, as assessed from the expansion of IFN-gamma(+) CD8(+) T cells, CTL activity against Ag-pulsed targets, and the rejection of transplanted tumors expressing the cognate Ag. The enhancement of CD8 alpha(+) 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. The Journal of Immunology, 2010,184: 736-745.