The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice

J Clin Invest. 2012 May;122(5):1628-43. doi: 10.1172/JCI60660. Epub 2012 Apr 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • Apoptosis
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Cross-Priming*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Gene Knockout Techniques
  • Interferon-gamma / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Lectins, C-Type / physiology*
  • Lysosomes / metabolism
  • Lysosomes / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Necrosis / virology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology*
  • Syk Kinase
  • Vaccinia / immunology*
  • Vaccinia / pathology
  • Vaccinia virus / immunology*
  • Vaccinia virus / physiology
  • Viral Load


  • Antigens, Viral
  • Clec9a protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Receptors, Immunologic
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse