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 CD8alpha+ 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 CD8alpha+ 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.
Asano
Jumpei
J
Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
Tada
Hiroyuki
H
Onai
Nobuyuki
N
Sato
Taku
T
Horie
Yasuo
Y
Fujimoto
Yukari
Y
Fukase
Koichi
K
Suzuki
Akira
A
Mak
Tak W
TW
Ohteki
Toshiaki
T
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D008024:Ligands; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein