Artículo
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity
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
Fecha de publicación:
12/2016
Editorial:
Elsevier Science
Revista:
Cell Reports
ISSN:
2211-1247
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Immunity
,
Vav Proteins
,
Signalling
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Identificadores
Colecciones
Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Citación
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
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