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

Mariolina BrunoSimone KerstenJudith M BainMartin JaegerDiletta RosatiMichael D KruppaDouglas W LowmanPeter J RiceBridget GravesZuchao MaYue Ning JiaoAnuradha ChowdharyGeorge RenierisFrank L van de VeerdonkBart-Jan KullbergEvangelos J Giamarellos-BourboulisAlexander HoischenNeil A R GowAlistair J P BrownJacques F MeisDavid L WilliamsMihai M Netea
Published in: Nature microbiology (2020)
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.
Keyphrases
  • candida albicans
  • immune response
  • biofilm formation
  • gene expression
  • endothelial cells
  • single cell
  • adipose tissue
  • cell death
  • genome wide
  • toll like receptor
  • heat shock
  • pseudomonas aeruginosa