Host immune response against the emerging fungal pathogen Candida auris: transcriptional and functional insights

Candida auris is amongst the most important emerging fungal pathogens, yet mechanistic insights in its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune cell profiling to uncover innate anti-C. auris defense mechanisms. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared to C. albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through 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 defense and identify possible targets for adjuvant immunotherapy. RNAsequencing profiles of PBMCs stimulated for 4h and 24h with live C. albicans and C. auris and their cell wall components Treatment definitions: RPMI: media control calb_live : PBMCs stimulated with C. albicans live calb_man: PBMCs stimulated with C. albicans-purified mannan calb_bg: PBMCs stimulated with C. albicans-purified beta glucan caur_KTClive: PBMCs stimulated with C. auris live caur_KTCman: PBMCs stimulated with C. auris-purified mannan caur_KTCbg: PBMCs stimulated with C. auris-purified beta glucan