English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity

MPS-Authors
/persons/resource/persons141286

Yeroslaviz,  Assa
Habermann, Bianca / Computational Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons101406

Habermann,  Bianca
Habermann, Bianca / Computational Biology, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)

1-s2.0-S2211124716315741-main.pdf
(Publisher version), 3MB

Supplementary Material (public)

Roth_mmc1.pdf
(Supplementary material), 884KB

Roth_mmc2.pdf
(Supplementary material), 4MB

Citation

Roth, S., Bergmann, H., Jaeger, M., Yeroslaviz, A., Neumann, K., Koenig, P.-A., et al. (2016). Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Reports, 17(10), 2572-2583. doi:10.1016/j.celrep.2016.11.018.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002C-F16D-4
Abstract
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-kB 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.