Iborra, SalvadorIzquierdo-Fernandez, Helena MariaMartinez-Lopez, MariaBlanco-Menendez, NoeliaReis e Sousa, CaetanoSancho, David2020-04-232020-04-232012-05J Clin Invest. 2012; 122(5):1628-430021-9738http://hdl.handle.net/20.500.12105/9713In order to prime T cells, DCs integrate signals emanating directly from pathogens and from their noxious action on the host. DNGR-1 (CLEC9A) is a DC-restricted receptor that detects dead cells. Therefore, we investigated the possibility that DNGR-1 affects immunity to cytopathic viruses. DNGR-1 was essential for cross-presentation of dying vaccinia virus-infected (VACV-infected) cells to CD8(+) T cells in vitro. Following injection of VACV or VACV-infected cells into mice, DNGR-1 detected the ligand in dying infected cells and mediated cross-priming of anti-VACV CD8(+) T cells. Loss of DNGR-1 impaired the CD8+ cytotoxic response to VACV, especially against those virus strains that are most dependent on cross-presentation. The decrease in total anti-VACV CTL activity was associated with a profound increase in viral load and delayed resolution of the primary lesion. In addition, lack of DNGR-1 markedly diminished protection from infection induced by vaccination with the modified vaccinia Ankara (MVA) strain. DNGR-1 thus contributes to anti-VACV immunity, following both primary infection and vaccination. The non-redundant ability of DNGR-1 to regulate cross-presentation of viral antigens suggests that this form of regulation of antiviral immunity could be exploited for vaccination.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Adaptive ImmunityAnimalsAntigen PresentationAntigens, ViralApoptosisCD8-Positive T-LymphocytesCells, CulturedDendritic CellsGene Knockout TechniquesInterferon-gammaAttribution-NonCommercial-NoDerivatives 4.0 Internacional2250545512251628-4310.1172/JCI606601558-8238The Journal of clinical investigationopen access