%0 Journal Article %T The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens %+ The Francis Crick Institute [London] %+ University of Manchester [Manchester] %+ Immunité et cancer (U932) %+ MRC Laboratory of Molecular Biology [Cambridge, UK] (LMB) %+ University of Cambridge [UK] (CAM) %+ Institut Curie [Paris] %+ Imperial College London %A Canton, Johnathan %A Blees, Hanna %A Henry, Conor %A Buck, Michael %A Schulz, Oliver %A Rogers, Neil %A Childs, Eleanor %A Zelenay, Santiago %A Rhys, Hefin %A Domart, Marie-Charlotte %A Collinson, Lucy %A Alloatti, Andres %A Ellison, Cara %A Amigorena, Sebastian %A Papayannopoulos, Venizelos %A Thomas, David %A Randow, Felix %A Reis E Sousa, Caetano %< avec comité de lecture %@ 1529-2908 %J Nature Immunology %I Nature Publishing Group %V 22 %N 2 %P 140-153 %8 2021-02 %D 2021 %R 10.1038/s41590-020-00824-x %M 3334970 %Z Life Sciences [q-bio]Journal articles %X Type 1 conventional dendritic (cDC1) cells are necessary for cross-presentation of many viral and tumor antigens to CD8+ T cells. cDC1 cells can be identified in mice and humans by high expression of DNGR-1 (also known as CLEC9A), a receptor that binds dead-cell debris and facilitates XP of corpse-associated antigens. Here, we show that DNGR-1 is a dedicated XP receptor that signals upon ligand engagement to promote phagosomal rupture. This allows escape of phagosomal contents into the cytosol, where they access the endogenous major histocompatibility complex class I antigen processing pathway. The activity of DNGR-1 maps to its signaling domain, which activates SYK and NADPH oxidase to cause phagosomal damage even when spliced into a heterologous receptor and expressed in heterologous cells. Our data reveal the existence of innate immune receptors that couple ligand binding to endocytic vesicle damage to permit MHC class I antigen presentation of exogenous antigens and to regulate adaptive immunity. %G English %L hal-03877502 %U https://cnrs.hal.science/hal-03877502 %~ INSERM %~ CNRS %~ FNCLCC %~ CURIE %~ PSL %~ INSTITUT-CURIE-PSL