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Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

A general procedure is described for the analysis of gene expression of Candida albicans cultured in a mouse infection model. This technique involves first infecting mice with Candida and subsequently harvesting blood and other tissue at specific time points during infection. The tissues are homogenized and the infecting Candida isolated. Finally, RNA is extracted from recovered Candida cells and subjected to microarray analysis.