SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans
Dectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through a hemITAM motif and couples sensing of pathogens such as fungi to induction of innate responses. Dectin-1 engagement triggers a plethora of activating events, but little is known about the modulation of such pathways....
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/9706 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/9706 |
| Access Level: | acceso abierto |
| Palabra clave: | Amino Acid Motifs Amino Acid Sequence Animals Blotting, Western Bone Marrow Cells Candida albicans Dendritic Cells Granulocyte-Macrophage Colony-Stimulating Factor Host-Pathogen Interactions Inositol Polyphosphate 5-Phosphatases Lectins, C-Type Macrophages Mice, Knockout Microscopy, Confocal Molecular Sequence Data NF-kappa B NFATC Transcription Factors Phagocytosis Phagosomes Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases Protein Binding Reactive Oxygen Species Signal Transduction |
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SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicansBlanco-Menendez, Noeliadel Fresno, CarlosFernandes, SandraCalvo, EnriqueConde-Garrosa, RuthKerr, William GSancho, DavidAmino Acid MotifsAmino Acid SequenceAnimalsBlotting, WesternBone Marrow CellsCandida albicansDendritic CellsGranulocyte-Macrophage Colony-Stimulating FactorHost-Pathogen InteractionsInositol Polyphosphate 5-PhosphatasesLectins, C-TypeMacrophagesMice, KnockoutMicroscopy, ConfocalMolecular Sequence DataNF-kappa BNFATC Transcription FactorsPhagocytosisPhagosomesPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesPhosphoric Monoester HydrolasesProtein BindingReactive Oxygen SpeciesSignal TransductionDectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through a hemITAM motif and couples sensing of pathogens such as fungi to induction of innate responses. Dectin-1 engagement triggers a plethora of activating events, but little is known about the modulation of such pathways. Trying to define a more precise picture of early Dectin-1 signaling, we explored the interactome of the intracellular tail of the receptor in mouse dendritic cells. We found unexpected binding of SHIP-1 phosphatase to the phosphorylated hemITAM. SHIP-1 colocalized with Dectin-1 during phagocytosis of zymosan in a hemITAM-dependent fashion. Moreover, endogenous SHIP-1 relocated to live or heat-killed Candida albicans-containing phagosomes in a Dectin-1-dependent manner in GM-CSF-derived bone marrow cells (GM-BM). However, SHIP-1 absence in GM-BM did not affect activation of MAPK or production of cytokines and readouts dependent on NF-κB and NFAT. Notably, ROS production was enhanced in SHIP-1-deficient GM-BM treated with heat-killed C. albicans, live C. albicans, or the specific Dectin-1 agonists curdlan or whole glucan particles. This increased oxidative burst was dependent on Dectin-1, Syk, PI3K, phosphoinositide-dependent protein kinase 1, and NADPH oxidase. GM-BM from CD11c∆SHIP-1 mice also showed increased killing activity against live C. albicans that was dependent on Dectin-1, Syk, and NADPH oxidase. These results illustrate the complexity of myeloid C-type lectin receptor signaling, and how an activating hemITAM can also couple to intracellular inositol phosphatases to modulate selected functional responses and tightly regulate processes such as ROS production that could be deleterious to the host.American Association of Immunologists (AAI)Ministerio de Economía y Competitividad (España)Unión Europea. Comisión Europea. European Research Council (ERC)Fundación ProCNICNational Institutes of Health (Estados Unidos)20202020-04-2320152015-11-0120152015-11-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/9706reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/97062026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| title |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| spellingShingle |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans Blanco-Menendez, Noelia Amino Acid Motifs Amino Acid Sequence Animals Blotting, Western Bone Marrow Cells Candida albicans Dendritic Cells Granulocyte-Macrophage Colony-Stimulating Factor Host-Pathogen Interactions Inositol Polyphosphate 5-Phosphatases Lectins, C-Type Macrophages Mice, Knockout Microscopy, Confocal Molecular Sequence Data NF-kappa B NFATC Transcription Factors Phagocytosis Phagosomes Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases Protein Binding Reactive Oxygen Species Signal Transduction |
| title_short |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| title_full |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| title_fullStr |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| title_full_unstemmed |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| title_sort |
SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans |
| dc.creator.none.fl_str_mv |
Blanco-Menendez, Noelia del Fresno, Carlos Fernandes, Sandra Calvo, Enrique Conde-Garrosa, Ruth Kerr, William G Sancho, David |
| author |
Blanco-Menendez, Noelia |
| author_facet |
Blanco-Menendez, Noelia del Fresno, Carlos Fernandes, Sandra Calvo, Enrique Conde-Garrosa, Ruth Kerr, William G Sancho, David |
| author_role |
author |
| author2 |
del Fresno, Carlos Fernandes, Sandra Calvo, Enrique Conde-Garrosa, Ruth Kerr, William G Sancho, David |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Economía y Competitividad (España) Unión Europea. Comisión Europea. European Research Council (ERC) Fundación ProCNIC National Institutes of Health (Estados Unidos) |
| dc.subject.none.fl_str_mv |
Amino Acid Motifs Amino Acid Sequence Animals Blotting, Western Bone Marrow Cells Candida albicans Dendritic Cells Granulocyte-Macrophage Colony-Stimulating Factor Host-Pathogen Interactions Inositol Polyphosphate 5-Phosphatases Lectins, C-Type Macrophages Mice, Knockout Microscopy, Confocal Molecular Sequence Data NF-kappa B NFATC Transcription Factors Phagocytosis Phagosomes Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases Protein Binding Reactive Oxygen Species Signal Transduction |
| topic |
Amino Acid Motifs Amino Acid Sequence Animals Blotting, Western Bone Marrow Cells Candida albicans Dendritic Cells Granulocyte-Macrophage Colony-Stimulating Factor Host-Pathogen Interactions Inositol Polyphosphate 5-Phosphatases Lectins, C-Type Macrophages Mice, Knockout Microscopy, Confocal Molecular Sequence Data NF-kappa B NFATC Transcription Factors Phagocytosis Phagosomes Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases Protein Binding Reactive Oxygen Species Signal Transduction |
| description |
Dectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through a hemITAM motif and couples sensing of pathogens such as fungi to induction of innate responses. Dectin-1 engagement triggers a plethora of activating events, but little is known about the modulation of such pathways. Trying to define a more precise picture of early Dectin-1 signaling, we explored the interactome of the intracellular tail of the receptor in mouse dendritic cells. We found unexpected binding of SHIP-1 phosphatase to the phosphorylated hemITAM. SHIP-1 colocalized with Dectin-1 during phagocytosis of zymosan in a hemITAM-dependent fashion. Moreover, endogenous SHIP-1 relocated to live or heat-killed Candida albicans-containing phagosomes in a Dectin-1-dependent manner in GM-CSF-derived bone marrow cells (GM-BM). However, SHIP-1 absence in GM-BM did not affect activation of MAPK or production of cytokines and readouts dependent on NF-κB and NFAT. Notably, ROS production was enhanced in SHIP-1-deficient GM-BM treated with heat-killed C. albicans, live C. albicans, or the specific Dectin-1 agonists curdlan or whole glucan particles. This increased oxidative burst was dependent on Dectin-1, Syk, PI3K, phosphoinositide-dependent protein kinase 1, and NADPH oxidase. GM-BM from CD11c∆SHIP-1 mice also showed increased killing activity against live C. albicans that was dependent on Dectin-1, Syk, and NADPH oxidase. These results illustrate the complexity of myeloid C-type lectin receptor signaling, and how an activating hemITAM can also couple to intracellular inositol phosphatases to modulate selected functional responses and tightly regulate processes such as ROS production that could be deleterious to the host. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-11-01 2015 2015-11-01 2020 2020-04-23 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 AM http://purl.org/coar/version/c_ab4af688f83e57aa |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12105/9706 |
| url |
http://hdl.handle.net/20.500.12105/9706 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
American Association of Immunologists (AAI) |
| publisher.none.fl_str_mv |
American Association of Immunologists (AAI) |
| dc.source.none.fl_str_mv |
reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
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Instituto de Salud Carlos III (ISCIII) |
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Repisalud |
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Repisalud |
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1869407644554362880 |
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15,811543 |