TLR3-Mediated CD8+ Dendritic Cell Activation Is Coupled with Establishment of a Cell-Intrinsic Antiviral State.

Autor:	Széles L; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland;, Meissner F; Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany;, Dunand-Sauthier I; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland;, Thelemann C; Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland;, Hersch M; Computational Biology Group, Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland; and., Singovski S; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland;, Haller S; Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland;, Gobet F; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland;, Fuertes Marraco SA; Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland;, Mann M; Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany;, Garcin D; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland., Acha-Orbea H; Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland;, Reith W; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland; Walter.Reith@unige.ch.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Aug 01; Vol. 195 (3), pp. 1025-33. Date of Electronic Publication: 2015 Jun 22.
DOI:	10.4049/jimmunol.1402033
Abstrakt:	Because of their unique capacity to cross-present Ags to CD8(+) T cells, mouse lymphoid tissue-resident CD8(+) dendritic cells (DCs) and their migratory counterparts are critical for priming antiviral T cell responses. High expression of the dsRNA sensor TLR3 is a distinctive feature of these cross-presenting DC subsets. TLR3 engagement in CD8(+) DCs promotes cross-presentation and the acquisition of effector functions required for driving antiviral T cell responses. In this study, we performed a comprehensive analysis of the TLR3-induced antiviral program and cell-autonomous immunity in CD8(+) DC lines and primary CD8(+) DCs. We found that TLR3-ligand polyinosinic-polycytidylic acid and human rhinovirus infection induced a potent antiviral protection against Sendai and vesicular stomatitis virus in a TLR3 and type I IFN receptor-dependent manner. Polyinosinic-polycytidylic acid-induced antiviral genes were identified by mass spectrometry-based proteomics and transcriptomics in the CD8(+) DC line. Nanostring nCounter experiments confirmed that these antiviral genes were induced by TLR3 engagement in primary CD8(+) DCs, and indicated that many are secondary TLR3-response genes requiring autocrine IFN-β stimulation. TLR3-activation thus establishes a type I IFN-dependent antiviral program in a DC subtype playing crucial roles in priming adaptive antiviral immune responses. This mechanism is likely to shield the priming of antiviral responses against inhibition or abrogation by the viral infection. It could be particularly relevant for viruses detected mainly by TLR3, which may not trigger type I IFN production by DCs that lack TLR3, such as plasmacytoid DCs or CD8(-) DCs. (Copyright © 2015 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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