title: The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice.
abstract: 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.
authors.affiliation: Immunobiology of Inflammation Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Iborra
authors.forename: Helena M
authors.initials: HM
authors.lastname: Izquierdo
authors.forename: María
authors.initials: M
authors.lastname: Martínez-López
authors.forename: Noelia
authors.initials: N
authors.lastname: Blanco-Menéndez
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.forename: David
authors.initials: D
authors.lastname: Sancho
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D055786:Gene Knockout Techniques; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009336:Necrosis / Q000821:virology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000072377:Syk Kinase; D014615:Vaccinia / Q000276:immunology* / Q000473:pathology; D014616:Vaccinia virus / Q000276:immunology* / Q000502:physiology; D019562:Viral Load
chemical_list: D000956:Antigens, Viral; C529914:Clec9a protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse