Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

Mariolina Bruno* (Corresponding Author), Simone Kersten, Judith M. Bain, Martin Jaeger, Diletta Rosati, Michael D Kruppa, Douglas W. Lowman, Peter J. Rice, Bridget Graves, Ma Zuchao, Y. Ning Jiao, Anuradha Chowdhary, George Renieris, Frank L van de Veerdonk, Bart-Jan Kullberg, Evangelos J. Giamarellos-Bourboulis, Alexander Hoischen, Neil A.R. Gow, Alistair J.P. Brown, Jacques F. MeisDavid L Williams, Mihai G. Netea*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalNature Microbiology
Early online date24 Aug 2020
DOIs
Publication statusE-pub ahead of print - 24 Aug 2020

Keywords

  • fungal host response
  • fungal infection
  • YEAST
  • SURVIVAL
  • LECTIN
  • RECOGNITION
  • ALBICANS
  • MANNAN
  • RESISTANT CANDIDA-AURIS
  • EMERGENCE
  • GLUCAN
  • BLOOD

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    Bruno, M., Kersten, S., Bain, J. M., Jaeger, M., Rosati, D., Kruppa, M. D., Lowman, D. W., Rice, P. J., Graves, B., Zuchao, M., Ning Jiao, Y., Chowdhary, A., Renieris, G., van de Veerdonk, F. L., Kullberg, B-J., Giamarellos-Bourboulis, E. J., Hoischen, A., Gow, N. A. R., Brown, A. J. P., ... Netea, M. G. (2020). Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris. Nature Microbiology. https://doi.org/10.1038/s41564-020-0780-3