The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens

Canton, Johnathan; Blees, Hanna; Henry, Conor M.; Buck, Michael D.; Schulz, Oliver; Rogers, Neil C.; Childs, Eleanor; Zelenay, Santiago; Rhys, Hefin; Domart, Marie-Charlotte; Collinson, Lucy; Alloatti, Andrés; Ellison, Cara J.; Amigorena, Sebastián; Papayannopoulos, Venizelos; Thomas, David; Randow, Felix; Sousa, Caetano Reis e

doi:10.1038/s41590-020-00824-x

Cited by 120 publications

(137 citation statements)

References 59 publications

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“…Thus, sGSN can dictate the degree to which tumor antigenicity is revealed to the CD8 + T cell compartment by cDC1s via DNGR-1-mediated cross-presentation. DNGR-1 functions in cDC1s by recognizing F-actin on necrotic cargo and signaling to promote phagosomal rupture, with consequent access of dead cell-associated antigens to the cytosolic MHC class I antigen processing pathway (Canton et al, 2021). Rupture is determined in part by the extent of DNGR-1 triggering and therefore is expected to be biased toward phagosomes containing debris with the highest actin cytoskeletal content.…”

Section: Discussionmentioning

confidence: 99%

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Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity

Giampazolias

Schulz

Lim

et al. 2021

Cell

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Section: Discussionmentioning

confidence: 99%

“…See also Figure S3. (Canton et al, 2021). To assess this directly, we sorted migratory cDC1s from the tdLNs of mice bearing B16F10 LA-OVA-mCherry tumors and co-cultured them with naive OVA-specific OT-I CD8 + T cells.…”

Section: Sgsn Reduces Dngr-1 Triggering and Crosspresentation Of Cellmentioning

confidence: 99%

Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity

Giampazolias

Schulz

Lim

et al. 2021

Cell

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“…In DC1s, however, extracellular antigens are released from phagosomes to the cytosol and then translocated via TAP (transfer associated with antigen processing) molecules to the endoplasmic reticulum (ER) where extracellular antigen peptides as well as intracellular antigen peptides are associated with MHCI [ 44 , 45 ]. Regarding the unusual pathway of extracellular antigens from phagosomes to cytosol, it has been recently reported that DNGR-1 (also known as CLEC9A) senses necrotic cell-derived F-actin [ 46 , 47 ] and its hemITAM-Syk signaling induces phagosomal membrane rupture to allow endocytosed antigens to enter the cytosol in DC1s [ 48 ].…”

Section: Tumormentioning

confidence: 99%

Shaping of T Cell Functions by Trogocytosis

Nakayama

Hori

Toyoura

et al. 2021

Cells

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Trogocytosis is an active process whereby plasma membrane proteins are transferred from one cell to the other cell in a cell-cell contact-dependent manner. Since the discovery of the intercellular transfer of major histocompatibility complex (MHC) molecules in the 1970s, trogocytosis of MHC molecules between various immune cells has been frequently observed. For instance, antigen-presenting cells (APCs) acquire MHC class I (MHCI) from allografts, tumors, and virally infected cells, and these APCs are subsequently able to prime CD8+ T cells without antigen processing via the preformed antigen-MHCI complexes, in a process called cross-dressing. T cells also acquire MHC molecules from APCs or other target cells via the immunological synapse formed at the cell-cell contact area, and this phenomenon impacts T cell activation. Compared with naïve and effector T cells, T regulatory cells have increased trogocytosis activity in order to remove MHC class II and costimulatory molecules from APCs, resulting in the induction of tolerance. Accumulating evidence suggests that trogocytosis shapes T cell functions in cancer, transplantation, and during microbial infections. In this review, we focus on T cell trogocytosis and the related inflammatory diseases.

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“…cDC1s have a high intrinsic capacity to cross-present antigens, due to the expression of the CLEC9A c-type lectin ( 12 ), and activate CD8 + , Th1 and NK cells ( 13 ). Myeloid cDC2s express different Pattern Recognition Receptors (PRRs) and can promote a wide range of immune responses and especially CD4 + T cell responses ( 14 ).…”

Section: Main Textmentioning

confidence: 99%

Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing

Marongiu

Protti

et al. 2021

Preprint

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Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, and this adversely affects T cell activation. Here, we find that cDC2 subtypes show similar infection-induced gene signatures with an increasing gradient of expression of interferon-stimulated genes from mild to severe patients and a down-regulation of major histocompatibility complex class II (MHC class II) molecules and some inflammatory cytokines compared to the baseline level of healthy donors. In vitro, the direct exposure of cDC2s to the virus recapitulates the type of activation observed in vivo. Our findings provide evidence that SARS-CoV-2 can directly interact with cDC2s and, by down-regulating crucial molecules required for T cell activation, implements an efficient immune escape mechanism.

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The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens

Cited by 120 publications

References 59 publications

Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity

Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity

Shaping of T Cell Functions by Trogocytosis

Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing

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