| First Author | Roth S | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 10 | Pages | 2572-2583 |
| PubMed ID | 27926862 | Mgi Jnum | J:241674 |
| Mgi Id | MGI:5903359 | Doi | 10.1016/j.celrep.2016.11.018 |
| Citation | Roth S, et al. (2016) Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Rep 17(10):2572-2583 |
| abstractText | 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-kappaB 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. |
