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.
We would like to thank Trees Jansen for performing the initial pilot experiments and Ilse Curfs-Breuker and Dirk Faro for their support at the CWZ hospital. We thank Charlotte Kaffa, BSc. for her technical assistance. We would like to thank Vinod Kumar for his input during the transcriptomic data analysis, Mark Gresnigt for the in vitro experimental suggestions and Anouk Becker for the help during the revision experiments. AJPB and NARG thank the MRC (MR/M026663/1) and Wellcome for support and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1). A.H. and S.K. were supported by the Radboud Institute for Molecular Life Sciences. Part of the study was supported by the Hellenic Institute for the Study of Sepsis. D.L.W. was supported by National Institutes of Health grants NIH GM083016, GM119197 and C06RR0306551. M.G.N. was supported by an ERC Advanced Grant (no. 833247) and a Spinoza Grant from the Netherlands Organization for Scientific Research.
- fungal host response
- fungal infection
- RESISTANT CANDIDA-AURIS