Immune cells fold and damage fungal hyphae

Jude Bain, Fernanda Alonso, Delma Childers, Catriona Walls, Kevin MacKenzie, Arnab Pradhan, Leanne E Lewis, Johanna Louw, Gabriela M Avelar, Daniel E Larcombe, Mihai G. Netea, Neil A.R. Gow, Gordon D Brown, Lars Erwig, Alistair J.P. Brown* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
4 Downloads (Pure)

Abstract

Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion, because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans-macrophage interactions we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin-myosin polymerisation and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance towards successful fungal clearance.
Original languageEnglish
Article numbere2020484118
Number of pages8
JournalPNAS
Volume118
Issue number15
Early online date5 Apr 2021
DOIs
Publication statusPublished - 13 Apr 2021

Bibliographical note

Acknowledgements
We thank Ben Rutter and Alex Brand for providing Mycelia sterilia hyphae, and Gillian Griffiths for insightful advice. We are grateful to the Microscopy and Histology Core Facility at the University of Aberdeen for their help, advice and support. This work was funded by grants from the UK Medical Research Council [www.mrc.ac.uk], to AJPB, NARG, LPE, MN (MR/M026663/1, MR/M026663/2), and from the University of Aberdeen to AP, DL. The work was also supported by Wellcome [www.wellcome.ac.uk]: NARG, GDB, AJPB (097377); NARG (101873, 200208); and GDB (102705). Further support for this work was also provided by the Medical Research Council Centre for Medical Mycology (MR/N006364/1).
MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords

  • Macrophages
  • fungal hyphae
  • mechanical force
  • immunological synapse
  • podosomes
  • cytoskeleton

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