Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/9713
The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice
Iborra, Salvador CNIC | Izquierdo-Fernandez, Helena Maria CNIC | Martinez-Lopez, Maria CNIC | Blanco-Menendez, Noelia CNIC | Reis e Sousa, Caetano | Sancho, David CNIC
J Clin Invest. 2012; 122(5):1628-43
In 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.
Adaptive Immunity | Animals | Antigen Presentation | Antigens, Viral | Apoptosis | CD8-Positive T-Lymphocytes | Cells, Cultured | Dendritic Cells | Gene Knockout Techniques | Interferon-gamma | Intracellular Signaling Peptides and Proteins | Lectins, C-Type | Lysosomes | Mice | Mice, Inbred C57BL | Mice, Transgenic | Necrosis | Protein-Tyrosine Kinases | Receptors, Immunologic | Syk Kinase | Vaccinia | Vaccinia virus | Viral Load | Cross-Priming
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