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

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-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

SUBMITTER: Roth S 

PROVIDER: S-EPMC5177621 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature