| First Author | Crespo MI | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 3 | Pages | 948-60 |
| PubMed ID | 23284054 | Mgi Jnum | J:193025 |
| Mgi Id | MGI:5467436 | Doi | 10.4049/jimmunol.1102725 |
| Citation | Crespo MI, et al. (2013) TLR7 triggering with polyuridylic acid promotes cross-presentation in CD8alpha+ conventional dendritic cells by enhancing antigen preservation and MHC class I antigen permanence on the dendritic cell surface. J Immunol 190(3):948-60 |
| abstractText | 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 CD8alpha(+) 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 CD8alpha(+) DCs treated with polyU, as well as by upregulation of costimulatory molecules and increased secretion of proinflammatory cytokines by DCs. Cross-priming 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. |
