期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 3, 页码 948-960出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1102725
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资金
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 2004-26339]
- Fundacion Antorchas
- Consejo Nacional de Investigaciones Cientificas y Tecnicas de Argentina [CONICET-PIP 5750, 11220090100109]
- Secretaria de Ciencia y Tecnologia
- Universidad Nacional de Cordoba
- Fundacion Florencio Fiorini
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.
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