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

CRESPO MI, ZACCA ER, NÚÑEZ NG, RANOCCHIA RP, MACCIONI M, MALETTO BA, PISTORESI-PALENCIA MC, MORÓN G.

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2013 p. 948 - 948

sRNA 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 CD8α(+) 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 CD8α(+) 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