TLR7 Triggering with Polyuridylic Acid Promotes Cross-Presentation in CD8α+ Conventional Dendritic Cells by Enhancing Antigen Preservation and MHC Class I Antigen Permanence on the Dendritic Cell Surface
TLR7 Triggering with Polyuridylic Acid Promotes Cross-Presentation in CD8α+ Conventional Dendritic Cells by Enhancing Antigen Preservation and MHC Class I Antigen Permanence on the Dendritic Cell Surface
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DOI：
10.4049/jimmunol.1102725
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发表时间：
2013-02-01
影响因子：
4.4
通讯作者：
Moron, Gabriel
中科院分区：
文献类型：
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作者：
Crespo, Maria I.;Zacca, Estefania R.;Moron, Gabriel
ssRNA通过与TLR7结合与树突状细胞相互作用，诱导促炎细胞因子和I型IFN的分泌。触发TLR7可增强CD8(+) T细胞的交叉启动，这需要将外源Ag交叉呈递到dc。然而，TLR触发如何影响Ag交叉呈现尚不清楚。利用OVA作为Ag模型，我们观察到多尿苷酸（polyU）（一种合成的ssRNA类似物）刺激dc中的TLR7，在C57BL/6小鼠中产生强烈的特异性细胞毒反应。理大刺激CD8 α (+) dc以I型ifn依赖的方式交叉初始CD8(+) T细胞。这种增强的交叉启动伴随着poly - u处理的CD8 α (+) dc上更高密度的OVA(256-264)/H-2K(b)复合物，以及dc共刺激分子的上调和促炎细胞因子的分泌增加。经polyU处理的dc交叉转染CD8(+) T细胞需要蛋白酶体和银通过dc中的Sec61通道转运到细胞质中。在dc中观察到的OVA与polyU交叉呈递的增强可能是由于吞噬体腔室中有限的Ag降解和dc上OVA肽/MHC I类复合物的更高持久性。这些观察结果清楚地表明，交叉呈递的银加工的关键步骤可以由TLR配体调节，为理解它们作为免疫应答佐剂的机制开辟了新的途径。免疫学杂志，2013,19:948-960。
ssRNA can interact with dendritic cells (DCs) through binding to TLR7, inducing secretion of proinflammatory cytokines and type I IFN. Triggering TLR7 enhances cross-priming of CD8(+) T cells, which requires cross-presentation of exogenous Ag to DCs. However, how TLR triggering can affect Ag cross-presentation is still not clear. Using OVA as an Ag model, we observed that stimulation of TLR7 in DCs by polyuridylic acid (polyU), a synthetic ssRNA analog, generates a strong specific cytotoxic response in C57BL/6 mice. PolyU stimulate CD8 alpha(+) DCs to cross-prime naive CD8(+) T cells in a type I IFN-dependent fashion. This enhanced cross-priming is accompanied by a higher density of OVA(256-264)/H-2K(b) complexes on CD8 alpha(+) DCs treated with polyU, as well as by upregulation of costimulatory molecules and increased secretion of proinflammatory cytokines by DCs. Crosspriming of CD8(+) T cells by DCs treated with polyU requires proteasome and Ag translocation to cytosol through the Sec61 channel in DCs. The observed enhancement in OVA cross-presentation with polyU in DCs could be mediated by a limited Ag degradation in endophagosomal compartments and a higher permanence of OVA peptide/MHC class I complexes on DCs. These observations clearly reveal that key steps of Ag processing for cross-presentation can be modulated by TLR ligands, opening new avenues for understanding their mechanisms as adjuvants of the immune response. The Journal of Immunology, 2013, 190: 948-960.