Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1

Mohlopheni J Marakalala, Simon Vautier, Joanna Potrykus, Louise A Walker, Kelly M Shepardson, Alex Hopke, Hector M Mora-Montes, Keunsook Lee, Ann Kerrigan, Mihai G Netea, Graeme I Murray, Donna M Maccallum, Robert Wheeler, Carol A Munro, Neil A R Gow, Robert A Cramer, Alistair J P Brown, Gordon D Brown

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Abstract

The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.

Original languageEnglish
Article numbere1003315
Number of pages12
JournalPLoS Pathogens
Volume9
Issue number4
DOIs
Publication statusPublished - 2013

Fingerprint

Candida albicans
Infection
Cell Wall
C-Type Lectins
Pattern Recognition Receptors
Chitin
Glucans
Immune System
Immunity
Fungi
dectin 1
Phenotype
Therapeutics
Pharmaceutical Preparations

Keywords

  • Animals
  • Antifungal Agents
  • Candida albicans
  • Cell Wall
  • Chitin
  • Echinocandins
  • Lectins, C-Type
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Pattern Recognition
  • beta-Glucans

Cite this

Marakalala, M. J., Vautier, S., Potrykus, J., Walker, L. A., Shepardson, K. M., Hopke, A., ... Brown, G. D. (2013). Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1. PLoS Pathogens, 9(4), [e1003315]. https://doi.org/10.1371/journal.ppat.1003315

Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1. / Marakalala, Mohlopheni J; Vautier, Simon; Potrykus, Joanna; Walker, Louise A; Shepardson, Kelly M; Hopke, Alex; Mora-Montes, Hector M; Lee, Keunsook; Kerrigan, Ann; Netea, Mihai G; Murray, Graeme I; Maccallum, Donna M; Wheeler, Robert; Munro, Carol A; Gow, Neil A R; Cramer, Robert A; Brown, Alistair J P; Brown, Gordon D.

In: PLoS Pathogens, Vol. 9, No. 4, e1003315, 2013.

Research output: Contribution to journalArticle

Marakalala, MJ, Vautier, S, Potrykus, J, Walker, LA, Shepardson, KM, Hopke, A, Mora-Montes, HM, Lee, K, Kerrigan, A, Netea, MG, Murray, GI, Maccallum, DM, Wheeler, R, Munro, CA, Gow, NAR, Cramer, RA, Brown, AJP & Brown, GD 2013, 'Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1', PLoS Pathogens, vol. 9, no. 4, e1003315. https://doi.org/10.1371/journal.ppat.1003315
Marakalala MJ, Vautier S, Potrykus J, Walker LA, Shepardson KM, Hopke A et al. Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1. PLoS Pathogens. 2013;9(4). e1003315. https://doi.org/10.1371/journal.ppat.1003315
Marakalala, Mohlopheni J ; Vautier, Simon ; Potrykus, Joanna ; Walker, Louise A ; Shepardson, Kelly M ; Hopke, Alex ; Mora-Montes, Hector M ; Lee, Keunsook ; Kerrigan, Ann ; Netea, Mihai G ; Murray, Graeme I ; Maccallum, Donna M ; Wheeler, Robert ; Munro, Carol A ; Gow, Neil A R ; Cramer, Robert A ; Brown, Alistair J P ; Brown, Gordon D. / Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1. In: PLoS Pathogens. 2013 ; Vol. 9, No. 4.
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