Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.

Candida albicans is a major life-threatening human fungal pathogen. Host defence against systemic Candida infection relies mainly on phagocytosis of fungal cells by cells of the innate immune system. In this study, we have employed video microscopy, coupled with sophisticated image analysis tools, t...

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Main Authors: Leanne E Lewis, Judith M Bain, Christina Lowes, Collette Gillespie, Fiona M Rudkin, Neil A R Gow, Lars-Peter Erwig
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002578&type=printable
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author Leanne E Lewis
Judith M Bain
Christina Lowes
Collette Gillespie
Fiona M Rudkin
Neil A R Gow
Lars-Peter Erwig
author_facet Leanne E Lewis
Judith M Bain
Christina Lowes
Collette Gillespie
Fiona M Rudkin
Neil A R Gow
Lars-Peter Erwig
author_sort Leanne E Lewis
collection DOAJ
description Candida albicans is a major life-threatening human fungal pathogen. Host defence against systemic Candida infection relies mainly on phagocytosis of fungal cells by cells of the innate immune system. In this study, we have employed video microscopy, coupled with sophisticated image analysis tools, to assess the contribution of distinct C. albicans cell wall components and yeast-hypha morphogenesis to specific stages of phagocytosis by macrophages. We show that macrophage migration towards C. albicans was dependent on the glycosylation status of the fungal cell wall, but not cell viability or morphogenic switching from yeast to hyphal forms. This was not a consequence of differences in maximal macrophage track velocity, but stems from a greater percentage of macrophages pursuing glycosylation deficient C. albicans during the first hour of the phagocytosis assay. The rate of engulfment of C. albicans attached to the macrophage surface was significantly delayed for glycosylation and yeast-locked morphogenetic mutant strains, but enhanced for non-viable cells. Hyphal cells were engulfed at a slower rate than yeast cells, especially those with hyphae in excess of 20 µm, but there was no correlation between hyphal length and the rate of engulfment below this threshold. We show that spatial orientation of the hypha and whether hyphal C. albicans attached to the macrophage via the yeast or hyphal end were also important determinants of the rate of engulfment. Breaking down the overall phagocytic process into its individual components revealed novel insights into what determines the speed and effectiveness of C. albicans phagocytosis by macrophages.
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spelling doaj-art-2b1e0b6bca974a3a937a909bcf9ca3852025-08-20T02:05:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0183e100257810.1371/journal.ppat.1002578Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.Leanne E LewisJudith M BainChristina LowesCollette GillespieFiona M RudkinNeil A R GowLars-Peter ErwigCandida albicans is a major life-threatening human fungal pathogen. Host defence against systemic Candida infection relies mainly on phagocytosis of fungal cells by cells of the innate immune system. In this study, we have employed video microscopy, coupled with sophisticated image analysis tools, to assess the contribution of distinct C. albicans cell wall components and yeast-hypha morphogenesis to specific stages of phagocytosis by macrophages. We show that macrophage migration towards C. albicans was dependent on the glycosylation status of the fungal cell wall, but not cell viability or morphogenic switching from yeast to hyphal forms. This was not a consequence of differences in maximal macrophage track velocity, but stems from a greater percentage of macrophages pursuing glycosylation deficient C. albicans during the first hour of the phagocytosis assay. The rate of engulfment of C. albicans attached to the macrophage surface was significantly delayed for glycosylation and yeast-locked morphogenetic mutant strains, but enhanced for non-viable cells. Hyphal cells were engulfed at a slower rate than yeast cells, especially those with hyphae in excess of 20 µm, but there was no correlation between hyphal length and the rate of engulfment below this threshold. We show that spatial orientation of the hypha and whether hyphal C. albicans attached to the macrophage via the yeast or hyphal end were also important determinants of the rate of engulfment. Breaking down the overall phagocytic process into its individual components revealed novel insights into what determines the speed and effectiveness of C. albicans phagocytosis by macrophages.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002578&type=printable
spellingShingle Leanne E Lewis
Judith M Bain
Christina Lowes
Collette Gillespie
Fiona M Rudkin
Neil A R Gow
Lars-Peter Erwig
Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
PLoS Pathogens
title Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
title_full Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
title_fullStr Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
title_full_unstemmed Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
title_short Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
title_sort stage specific assessment of candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002578&type=printable
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