Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity
- Autores
- Roth, Susanne; Bergmann, Hanna; Jaeger, Martin; Yeroslaviz, Assa; Neumann, Konstantin; Koenig, Paul Albert; Prazeres da Costa, Clarissa; Vanes, Lesley; Kumar, Vinod; Johnson, Melissa; Menacho Márquez, Mauricio Ariel; Habermann, Bianca; Tybulewicz, Victor L.; Netea, Mihai; Bustelo, Xosé R.; Ruland, Jürgen
- Año de publicación
- 2016
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription. Although Vav family members show functional redundancy, Vav1/2/3−/− mice phenocopy Card9−/− animals with extreme susceptibility to fungi. In this context, Vav3 is the single most important Vav in mice, and a polymorphism in human VAV3 is associated with susceptibility to candidemia in patients. Our results reveal a molecular mechanism for CLR-mediated Card9 regulation that controls innate immunity to fungal infections.
Fil: Roth, Susanne. Technische Universitat Munchen; Alemania
Fil: Bergmann, Hanna. Technische Universitat Munchen; Alemania
Fil: Jaeger, Martin. Radboud Universiteit Nijmegen; Países Bajos
Fil: Yeroslaviz, Assa. Max Planck Institute Of Biochemistry.; Alemania
Fil: Neumann, Konstantin. Technische Universitat Munchen; Alemania
Fil: Koenig, Paul Albert. Technische Universitat Munchen; Alemania
Fil: Prazeres da Costa, Clarissa. Technische Universitat Munchen; Alemania
Fil: Vanes, Lesley. Francis Crick Institute; Reino Unido
Fil: Kumar, Vinod. University of Groningen; Países Bajos
Fil: Johnson, Melissa. University of Duke; Estados Unidos
Fil: Menacho Márquez, Mauricio Ariel. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Habermann, Bianca. Max Planck Institute Of Biochemistry.; Alemania
Fil: Tybulewicz, Victor L.. Francis Crick Institute; Reino Unido. Imperial College London; Reino Unido
Fil: Netea, Mihai. Radboud Universiteit Nijmegen; Países Bajos
Fil: Bustelo, Xosé R.. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Ruland, Jürgen. Technische Universitat Munchen; Alemania - Materia
-
Immunity
Vav Proteins
Signalling - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/51305
Ver los metadatos del registro completo
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Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal ImmunityRoth, SusanneBergmann, HannaJaeger, MartinYeroslaviz, AssaNeumann, KonstantinKoenig, Paul AlbertPrazeres da Costa, ClarissaVanes, LesleyKumar, VinodJohnson, MelissaMenacho Márquez, Mauricio ArielHabermann, BiancaTybulewicz, Victor L.Netea, MihaiBustelo, Xosé R.Ruland, JürgenImmunityVav ProteinsSignallinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription. Although Vav family members show functional redundancy, Vav1/2/3−/− mice phenocopy Card9−/− animals with extreme susceptibility to fungi. In this context, Vav3 is the single most important Vav in mice, and a polymorphism in human VAV3 is associated with susceptibility to candidemia in patients. Our results reveal a molecular mechanism for CLR-mediated Card9 regulation that controls innate immunity to fungal infections.Fil: Roth, Susanne. Technische Universitat Munchen; AlemaniaFil: Bergmann, Hanna. Technische Universitat Munchen; AlemaniaFil: Jaeger, Martin. Radboud Universiteit Nijmegen; Países BajosFil: Yeroslaviz, Assa. Max Planck Institute Of Biochemistry.; AlemaniaFil: Neumann, Konstantin. Technische Universitat Munchen; AlemaniaFil: Koenig, Paul Albert. Technische Universitat Munchen; AlemaniaFil: Prazeres da Costa, Clarissa. Technische Universitat Munchen; AlemaniaFil: Vanes, Lesley. Francis Crick Institute; Reino UnidoFil: Kumar, Vinod. University of Groningen; Países BajosFil: Johnson, Melissa. University of Duke; Estados UnidosFil: Menacho Márquez, Mauricio Ariel. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Habermann, Bianca. Max Planck Institute Of Biochemistry.; AlemaniaFil: Tybulewicz, Victor L.. Francis Crick Institute; Reino Unido. Imperial College London; Reino UnidoFil: Netea, Mihai. Radboud Universiteit Nijmegen; Países BajosFil: Bustelo, Xosé R.. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Ruland, Jürgen. Technische Universitat Munchen; AlemaniaElsevier Science2016-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/51305Roth, Susanne; Bergmann, Hanna; Jaeger, Martin; Yeroslaviz, Assa; Neumann, Konstantin; et al.; Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity; Elsevier Science; Cell Reports; 17; 10; 12-2016; 2572-25832211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.11.018info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124716315741info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:59Zoai:ri.conicet.gov.ar:11336/51305instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:03:59.315CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
title |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
spellingShingle |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity Roth, Susanne Immunity Vav Proteins Signalling |
title_short |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
title_full |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
title_fullStr |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
title_full_unstemmed |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
title_sort |
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity |
dc.creator.none.fl_str_mv |
Roth, Susanne Bergmann, Hanna Jaeger, Martin Yeroslaviz, Assa Neumann, Konstantin Koenig, Paul Albert Prazeres da Costa, Clarissa Vanes, Lesley Kumar, Vinod Johnson, Melissa Menacho Márquez, Mauricio Ariel Habermann, Bianca Tybulewicz, Victor L. Netea, Mihai Bustelo, Xosé R. Ruland, Jürgen |
author |
Roth, Susanne |
author_facet |
Roth, Susanne Bergmann, Hanna Jaeger, Martin Yeroslaviz, Assa Neumann, Konstantin Koenig, Paul Albert Prazeres da Costa, Clarissa Vanes, Lesley Kumar, Vinod Johnson, Melissa Menacho Márquez, Mauricio Ariel Habermann, Bianca Tybulewicz, Victor L. Netea, Mihai Bustelo, Xosé R. Ruland, Jürgen |
author_role |
author |
author2 |
Bergmann, Hanna Jaeger, Martin Yeroslaviz, Assa Neumann, Konstantin Koenig, Paul Albert Prazeres da Costa, Clarissa Vanes, Lesley Kumar, Vinod Johnson, Melissa Menacho Márquez, Mauricio Ariel Habermann, Bianca Tybulewicz, Victor L. Netea, Mihai Bustelo, Xosé R. Ruland, Jürgen |
author2_role |
author author author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Immunity Vav Proteins Signalling |
topic |
Immunity Vav Proteins Signalling |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription. Although Vav family members show functional redundancy, Vav1/2/3−/− mice phenocopy Card9−/− animals with extreme susceptibility to fungi. In this context, Vav3 is the single most important Vav in mice, and a polymorphism in human VAV3 is associated with susceptibility to candidemia in patients. Our results reveal a molecular mechanism for CLR-mediated Card9 regulation that controls innate immunity to fungal infections. Fil: Roth, Susanne. Technische Universitat Munchen; Alemania Fil: Bergmann, Hanna. Technische Universitat Munchen; Alemania Fil: Jaeger, Martin. Radboud Universiteit Nijmegen; Países Bajos Fil: Yeroslaviz, Assa. Max Planck Institute Of Biochemistry.; Alemania Fil: Neumann, Konstantin. Technische Universitat Munchen; Alemania Fil: Koenig, Paul Albert. Technische Universitat Munchen; Alemania Fil: Prazeres da Costa, Clarissa. Technische Universitat Munchen; Alemania Fil: Vanes, Lesley. Francis Crick Institute; Reino Unido Fil: Kumar, Vinod. University of Groningen; Países Bajos Fil: Johnson, Melissa. University of Duke; Estados Unidos Fil: Menacho Márquez, Mauricio Ariel. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina Fil: Habermann, Bianca. Max Planck Institute Of Biochemistry.; Alemania Fil: Tybulewicz, Victor L.. Francis Crick Institute; Reino Unido. Imperial College London; Reino Unido Fil: Netea, Mihai. Radboud Universiteit Nijmegen; Países Bajos Fil: Bustelo, Xosé R.. Consejo Superior de Investigaciones Científicas; España. Universidad de Salamanca; España. Universidad Carlos III de Madrid. Instituto de Salud; España Fil: Ruland, Jürgen. Technische Universitat Munchen; Alemania |
description |
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription. Although Vav family members show functional redundancy, Vav1/2/3−/− mice phenocopy Card9−/− animals with extreme susceptibility to fungi. In this context, Vav3 is the single most important Vav in mice, and a polymorphism in human VAV3 is associated with susceptibility to candidemia in patients. Our results reveal a molecular mechanism for CLR-mediated Card9 regulation that controls innate immunity to fungal infections. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/51305 Roth, Susanne; Bergmann, Hanna; Jaeger, Martin; Yeroslaviz, Assa; Neumann, Konstantin; et al.; Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity; Elsevier Science; Cell Reports; 17; 10; 12-2016; 2572-2583 2211-1247 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/51305 |
identifier_str_mv |
Roth, Susanne; Bergmann, Hanna; Jaeger, Martin; Yeroslaviz, Assa; Neumann, Konstantin; et al.; Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity; Elsevier Science; Cell Reports; 17; 10; 12-2016; 2572-2583 2211-1247 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.11.018 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124716315741 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Science |
publisher.none.fl_str_mv |
Elsevier Science |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |