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

Publication ,  Journal Article
Roth, S; Bergmann, H; Jaeger, M; Yeroslaviz, A; Neumann, K; Koenig, P-A; Prazeres da Costa, C; Vanes, L; Kumar, V; Johnson, M; Habermann, B ...
Published in: Cell Rep
December 6, 2016

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 6, 2016

Volume

17

Issue

10

Start / End Page

2572 / 2583

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proto-Oncogene Proteins c-vav
  • NF-kappa B
  • Mice
  • Membrane Proteins
  • Lectins, C-Type
  • Immunity, Innate
  • Humans
  • Candidemia
  • Candida
 

Citation

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Roth, S., Bergmann, H., Jaeger, M., Yeroslaviz, A., Neumann, K., Koenig, P.-A., … Ruland, J. (2016). Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Rep, 17(10), 2572–2583. https://doi.org/10.1016/j.celrep.2016.11.018
Roth, Susanne, Hanna Bergmann, Martin Jaeger, Assa Yeroslaviz, Konstantin Neumann, Paul-Albert Koenig, Clarissa Prazeres da Costa, et al. “Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity.Cell Rep 17, no. 10 (December 6, 2016): 2572–83. https://doi.org/10.1016/j.celrep.2016.11.018.
Roth S, Bergmann H, Jaeger M, Yeroslaviz A, Neumann K, Koenig P-A, et al. Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Rep. 2016 Dec 6;17(10):2572–83.
Roth, Susanne, et al. “Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity.Cell Rep, vol. 17, no. 10, Dec. 2016, pp. 2572–83. Pubmed, doi:10.1016/j.celrep.2016.11.018.
Roth S, Bergmann H, Jaeger M, Yeroslaviz A, Neumann K, Koenig P-A, Prazeres da Costa C, Vanes L, Kumar V, Johnson M, Menacho-Márquez M, Habermann B, Tybulewicz VL, Netea M, Bustelo XR, Ruland J. Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Rep. 2016 Dec 6;17(10):2572–2583.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 6, 2016

Volume

17

Issue

10

Start / End Page

2572 / 2583

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proto-Oncogene Proteins c-vav
  • NF-kappa B
  • Mice
  • Membrane Proteins
  • Lectins, C-Type
  • Immunity, Innate
  • Humans
  • Candidemia
  • Candida