title: The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice.
abstract: DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment, favoring cross-presentation to CD8(+) T cells. DNGR-1 regulated cross-priming in non-infectious settings such as immunization with antigen-bearing dead cells, as well as in highly immunogenic situations such as infection with herpes simplex virus type 1. Together, these results suggest that DNGR-1 is a dedicated receptor for cross-presentation of cell-associated antigens. Our work thus underscores the importance of cross-priming in immunity and indicates that antigenicity and adjuvanticity can be decoded by distinct innate immune receptors. The identification of specialized receptors that regulate antigenicity of virus-infected cells reveals determinants of antiviral immunity that might underlie the human response to infection and vaccination.
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK.
authors.forename: Santiago
authors.initials: S
authors.lastname: Zelenay
authors.forename: Anna M
authors.initials: AM
authors.lastname: Keller
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.forename: Barbara U
authors.initials: BU
authors.lastname: Schraml
authors.forename: Safia
authors.initials: S
authors.lastname: Deddouche
authors.forename: Neil C
authors.initials: NC
authors.lastname: Rogers
authors.forename: Oliver
authors.initials: O
authors.lastname: Schulz
authors.forename: David
authors.initials: D
authors.lastname: Sancho
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology / Q000473:pathology; D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000502:physiology; D009336:Necrosis / Q000378:metabolism* / Q000821:virology; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C529914:Clec9a protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D010047:Ovalbumin