Nucleotide Oligomerization Binding Domain-Like Receptor Signaling Enhances Dendritic Cell-Mediated Cross-Priming In Vivo
Nucleotide Oligomerization Binding Domain-Like Receptor Signaling Enhances Dendritic Cell-Mediated Cross-Priming In Vivo
复制标题
DOI：
10.4049/jimmunol.0900726
复制
发表时间：
2010-01-15
影响因子：
4.4
通讯作者：
Ohteki, Toshiaki
中科院分区：
文献类型：
--
作者：
Asano, Jumpei;Tada, Hiroyuki;Ohteki, Toshiaki
核苷酸寡聚化结合结构域（Nod）样受体是识别细菌肽聚糖的重要胞质传感器。然而，它们在诱导树突状细胞（DC）介导的交叉致敏中的作用仍不清楚。在这项研究中，我们证明了将Nod 1和Nod 2的配体沿着与Ag一起注射到野生型小鼠中显著增强了Ag特异性CD 8（+）T细胞与CD 8 α（+）DC的交叉致敏，如从IFN-γ（+）CD 8（+）T细胞的扩增、针对Ag脉冲靶的CTL活性以及表达同源Ag的移植肿瘤的排斥所评估的。CD 8 α（+）DC介导的交叉致敏的增强可能是由于Ag交叉呈递和共刺激分子的上调。我们的研究结果共同表明，Nod 1/2信号传导对于体内DC交叉引发的最佳诱导至关重要，这可能为癌症和TLR信号难治性或因病毒逃避策略而瘫痪的宿主提供替代治疗途径。免疫学杂志，2010，184：736-745.
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.