Adaptor protein CARD9 is required for systemic host defense against C andida auris.

Candida auris is a fungus that emerged as a public health concern with several outbreaks. Its ability to persist in human skin for prolonged periods induces a risk of invasive infection. C. auris has been suggested to activate innate immunity via C-type lectin receptors (CLRs). We found that mice lacking Card9, an adaptor protein for CLR signaling, were lethal upon systemic infection with C. auris. Card9 deficiency exhibited severe renal lesions and a marked increase in fungal load during infection, with impaired inflammatory cytokine production and attenuated T cell responses. Following infection, increased neutrophil cell death was observed in the kidneys of Card9 -/- mice. Treatment with commercially available antifungal drugs improved the survival of Card9 -/- mice systemically infected with C. auris. Our findings provide valuable insights into host defense mechanisms against invasive C. auris infection and will be useful for developing antifungal drugs and therapies against C. auris infection.