info:eu-repo/semantics/article
TLR7 triggering with Polyuridylic acid promotes cross-presentation in CD8a+ conventional dendritic cells by enhancing antigen preservation and MHC Class I antigen permanence on the dendritic cell surface
Fecha
2013-01Registro en:
Crespo, Maria Ines; Zacca, Estefanía; Núñez, Nicolás; Ranocchia, Romina Paola; Maccioni, Mariana; et al.; TLR7 triggering with Polyuridylic acid promotes cross-presentation in CD8a+ conventional dendritic cells by enhancing antigen preservation and MHC Class I antigen permanence on the dendritic cell surface; American Association of Immunologists; Journal of Immunology; 190; 3; 1-2013; 948-960
0022-1767
CONICET Digital
CONICET
Autor
Crespo, Maria Ines
Zacca, Estefanía
Núñez, Nicolás
Ranocchia, Romina Paola
Maccioni, Mariana
Maletto, Belkys Angélica
Pistoresi, Maria Cristina
Moron, Victor Gabriel
Resumen
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 CD8a+ 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 OVA256-264/H-2Kb complexes on CD8a+ 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.