Adaptor protein CARD9 is required for systemic host defense against Candida auris

<i>Candida auris</i> 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. <i>C. auris</i> 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 <i>C. auris</i>. 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 <i>Card9</i> ^-/- mice. Treatment with commercially available antifungal drugs improved the survival of <i>Card9</i> ^-/- mice systemically infected with <i>C. auris</i>. Our findings provide valuable insights into host defense mechanisms against invasive <i>C. auris</i> infection and will be useful for developing antifungal drugs and therapies against <i>C. auris</i> infection.