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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/51305
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/51305
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:33:46Zoai: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:34982025-10-22 11:33:47.248CONICET 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
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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