CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
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.
Autor/es:
CRESPO, MI; ZACCA, E; NUÑEZ, N; RANOCCHIA, R; MACCIONI, M; MALETTO, B; PISTORESI, MC; MORÓN, G
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
AMER ASSOC IMMUNOLOGISTS
Referencias:
Lugar: Bethesda; Año: 2013 vol. 190 p. 948 - 960
ISSN:
0022-1767
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