Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion

Arnab Pradhan, Gabriela M. Avelar, Judith M. Bain, Delma Childers, Chloe Pelletier, Daniel E. Larcombe, Elena Shekhova, Mihai G. Netea, Gordon D. Brown, Lars Erwig, Neil A. R. Gow, Alistair J. P. Brown* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)
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To colonise their host, pathogens must counter local environmental and immunological challenges. We reveal that the fungal pathogen, Candida albicans, exploits diverse host signals to promote immune evasion via masking of the major pathogen associated molecular pattern (PAMP), β-glucan. Certain nutrients, stresses and antifungal drugs trigger β-glucan masking, whereas other inputs, such as nitrogen sources and quorum sensing molecules, exert limited effects on this PAMP. In particular, iron limitation triggers dramatic changes in the cell wall that reduce β-glucan exposure. This correlates with reduced phagocytosis by macrophages and attenuated cytokine responses by peripheral blood mononuclear cells. Iron limitation-induced β-glucan masking depends on parallel signalling via the iron transceptor Ftr1 and iron-responsive transcription factor Sef1, and the protein kinase A pathway. Our data reveal that C. albicans exploits a diverse range of specific host signals to trigger protective anticipatory responses against impending phagocytic attack and promote host colonisation.
Original languageEnglish
Article number5315
Number of pages14
JournalNature Communications
Publication statusPublished - 22 Nov 2019

Bibliographical note

Data Availability
The authors declare that the data supporting the findings of this study are available within the paper (and its supplementary information files).

We are grateful to Raif Yuecel, Linda Duncan, Kimberley Sim and Ailsa Laird in the Iain Fraser Cytometry Centre, and to Kevin MacKenzie, Debbie Wilkinson, Gillian Milne and Lucy Wight in our Microscopy and Histology Core Facility for their superb support. We thank Katja Schafer and Angela Lopez for help with the design of primers and for providing CRISPR-Cas9 protocols for mutant construction. We also thank our colleagues in the Candida community, and in particular Jan Quinn, Guanghua Huang, Suzanne Noble, Karl Kuchler, Patrick van Dijck, Rich Calderone and Malcolm Whiteway for providing strains used in this study.
This work was funded by a programme grant from the UK Medical Research Council [ MR/M026663/1], and by PhD studentships from the University of Aberdeen to AP, DL. The work was also supported by the Medical Research Council Centre for Medical Mycology and the University of Aberdeen [MR/N006364/1], by the European Commission [FunHoMic: H2020-MSCA-ITN-2018-812969], and by the Wellcome Trust via Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards [ 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


  • Candida albicans
  • immune evasion
  • cell wall
  • pathogen associated molecular patterns
  • β-glucan
  • iron responses
  • Ftr1
  • Sef1
  • cAMP-protein kinase A signalling


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