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

doi:10.1073/pnas.2020484118

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 journal › Article › peer-review

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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 language	English
Article number	e2020484118
Number of pages	8
Journal	PNAS
Volume	118
Issue number	15
Early online date	5 Apr 2021
DOIs	https://doi.org/10.1073/pnas.2020484118
Publication status	Published - 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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10.1073/pnas.2020484118Licence: CC BY

Bain_etal_PNAS_Immune_Cells_Fold_VoR
Copyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/
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Cite this

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title = "Immune cells fold and damage fungal hyphae",

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.",

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author = "Jude Bain and Fernanda Alonso and Delma Childers and Catriona Walls and Kevin MacKenzie and Arnab Pradhan and Lewis, {Leanne E} and Johanna Louw and Avelar, {Gabriela M} and Larcombe, {Daniel E} and Netea, {Mihai G.} and Gow, {Neil A.R.} and Brown, {Gordon D} and Lars Erwig and Brown, {Alistair J.P.}",

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. ",

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AU - Bain, Jude

AU - Alonso, Fernanda

AU - Childers, Delma

AU - Walls, Catriona

AU - MacKenzie, Kevin

AU - Pradhan, Arnab

AU - Lewis, Leanne E

AU - Louw, Johanna

AU - Avelar, Gabriela M

AU - Larcombe, Daniel E

AU - Netea, Mihai G.

AU - Gow, Neil A.R.

AU - Brown, Gordon D

AU - Erwig, Lars

AU - Brown, Alistair J.P.

N1 - 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.

PY - 2021/4/13

Y1 - 2021/4/13

N2 - 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.

AB - 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.

KW - Macrophages

KW - fungal hyphae

KW - mechanical force

KW - immunological synapse

KW - podosomes

KW - cytoskeleton

U2 - 10.1073/pnas.2020484118

DO - 10.1073/pnas.2020484118

M3 - Article

SN - 0027-8424

VL - 118

JO - PNAS

JF - PNAS

IS - 15

M1 - e2020484118

ER -

Immune cells fold and damage fungal hyphae

Abstract

Bibliographical note

Keywords

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