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)

Research output: Contribution to journalArticle

Abstract

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
JournalNature Communications
Publication statusAccepted/In press - 9 Sep 2019

Fingerprint

Immune Evasion
Glucans
pathogens
Cell Wall
Iron
masking
Cells
iron
actuators
Pathogens
Candida albicans
Quorum Sensing
blood cells
macrophages
Candida
Macrophages
nutrients
Cyclic AMP-Dependent Protein Kinases
Phagocytosis
Nutrients

Keywords

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

Cite this

@article{6144b078894c4bbc925389e3d09c94e9,
title = "Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion",
abstract = "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.",
keywords = "Candida albicans, immune evasion, cell wall, pathogen associated molecular patterns, β-glucan, iron responses, Ftr1, Sef1, cAMP-protein kinase A signalling",
author = "Arnab Pradhan and Avelar, {Gabriela M.} and Bain, {Judith M.} and Delma Childers and Chloe Pelletier and Larcombe, {Daniel E.} and Elena Shekhova and Netea, {Mihai G.} and Brown, {Gordon D.} and Lars Erwig and Gow, {Neil A. R.} and Brown, {Alistair J. P.}",
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). Acknowledgements 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 [www.mrc.ac.uk: 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 [www.wellcome.ac.uk: 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.",
year = "2019",
month = "9",
day = "9",
language = "English",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion

AU - Pradhan, Arnab

AU - Avelar, Gabriela M.

AU - Bain, Judith M.

AU - Childers, Delma

AU - Pelletier, Chloe

AU - Larcombe, Daniel E.

AU - Shekhova, Elena

AU - Netea, Mihai G.

AU - Brown, Gordon D.

AU - Erwig, Lars

AU - Gow, Neil A. R.

AU - Brown, Alistair J. P.

N1 - Data Availability The authors declare that the data supporting the findings of this study are available within the paper (and its supplementary information files). Acknowledgements 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 [www.mrc.ac.uk: 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 [www.wellcome.ac.uk: 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.

PY - 2019/9/9

Y1 - 2019/9/9

N2 - 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.

AB - 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.

KW - Candida albicans

KW - immune evasion

KW - cell wall

KW - pathogen associated molecular patterns

KW - β-glucan

KW - iron responses

KW - Ftr1

KW - Sef1

KW - cAMP-protein kinase A signalling

M3 - Article

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -