<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation

ABSTRACT Candida albicans is a major life-threatening human fungal pathogen in the immunocompromised host. Host defense against systemic Candida infection relies heavily on the capacity of professional phagocytes of the innate immune system to ingest and destroy fungal cells. A number of pathogens,...

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Autores principales:	Judith M. Bain, Johanna Louw, Leanne E. Lewis, Blessing Okai, Catriona A. Walls, Elizabeth R. Ballou, Louise A. Walker, Delyth Reid, Carol A. Munro, Alistair J. P. Brown, Gordon D. Brown, Neil A. R. Gow, Lars P. Erwig
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/330d9e9e688940309c726a225cc2763d
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spelling	oai:doaj.org-article:330d9e9e688940309c726a225cc2763d2021-11-15T15:47:03Z<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation10.1128/mBio.01874-142150-7511https://doaj.org/article/330d9e9e688940309c726a225cc2763d2014-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01874-14https://doaj.org/toc/2150-7511ABSTRACT Candida albicans is a major life-threatening human fungal pathogen in the immunocompromised host. Host defense against systemic Candida infection relies heavily on the capacity of professional phagocytes of the innate immune system to ingest and destroy fungal cells. A number of pathogens, including C. albicans, have evolved mechanisms that attenuate the efficiency of phagosome-mediated inactivation, promoting their survival and replication within the host. Here we visualize host-pathogen interactions using live-cell imaging and show that viable, but not heat- or UV-killed C. albicans cells profoundly delay phagosome maturation in macrophage cell lines and primary macrophages. The ability of C. albicans to delay phagosome maturation is dependent on cell wall composition and fungal morphology. Loss of cell wall O-mannan is associated with enhanced acquisition of phagosome maturation markers, distinct changes in Rab GTPase acquisition by the maturing phagosome, impaired hyphal growth within macrophage phagosomes, profound changes in macrophage actin dynamics, and ultimately a reduced ability of fungal cells to escape from macrophage phagosomes. The loss of cell wall O-mannan leads to exposure of β-glucan in the inner cell wall, facilitating recognition by Dectin-1, which is associated with enhanced phagosome maturation. IMPORTANCE Innate cells engulf and destroy invading organisms by phagocytosis, which is essential for the elimination of fungal cells to protect against systemic life-threatening infections. Yet comparatively little is known about what controls the maturation of phagosomes following ingestion of fungal cells. We used live-cell microscopy and fluorescent protein reporter macrophages to understand how C. albicans viability, filamentous growth, and cell wall composition affect phagosome maturation and the survival of the pathogen within host macrophages. We have demonstrated that cell wall glycosylation and yeast-hypha morphogenesis are required for disruption of host processes that function to inactivate pathogens, leading to survival and escape of this fungal pathogen from within host phagocytes. The methods employed here are applicable to study interactions of other pathogens with phagocytic cells to dissect how specific microbial features impact different stages of phagosome maturation and the survival of the pathogen or host.Judith M. BainJohanna LouwLeanne E. LewisBlessing OkaiCatriona A. WallsElizabeth R. BallouLouise A. WalkerDelyth ReidCarol A. MunroAlistair J. P. BrownGordon D. BrownNeil A. R. GowLars P. ErwigAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 6 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Judith M. Bain Johanna Louw Leanne E. Lewis Blessing Okai Catriona A. Walls Elizabeth R. Ballou Louise A. Walker Delyth Reid Carol A. Munro Alistair J. P. Brown Gordon D. Brown Neil A. R. Gow Lars P. Erwig <named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation
description	ABSTRACT Candida albicans is a major life-threatening human fungal pathogen in the immunocompromised host. Host defense against systemic Candida infection relies heavily on the capacity of professional phagocytes of the innate immune system to ingest and destroy fungal cells. A number of pathogens, including C. albicans, have evolved mechanisms that attenuate the efficiency of phagosome-mediated inactivation, promoting their survival and replication within the host. Here we visualize host-pathogen interactions using live-cell imaging and show that viable, but not heat- or UV-killed C. albicans cells profoundly delay phagosome maturation in macrophage cell lines and primary macrophages. The ability of C. albicans to delay phagosome maturation is dependent on cell wall composition and fungal morphology. Loss of cell wall O-mannan is associated with enhanced acquisition of phagosome maturation markers, distinct changes in Rab GTPase acquisition by the maturing phagosome, impaired hyphal growth within macrophage phagosomes, profound changes in macrophage actin dynamics, and ultimately a reduced ability of fungal cells to escape from macrophage phagosomes. The loss of cell wall O-mannan leads to exposure of β-glucan in the inner cell wall, facilitating recognition by Dectin-1, which is associated with enhanced phagosome maturation. IMPORTANCE Innate cells engulf and destroy invading organisms by phagocytosis, which is essential for the elimination of fungal cells to protect against systemic life-threatening infections. Yet comparatively little is known about what controls the maturation of phagosomes following ingestion of fungal cells. We used live-cell microscopy and fluorescent protein reporter macrophages to understand how C. albicans viability, filamentous growth, and cell wall composition affect phagosome maturation and the survival of the pathogen within host macrophages. We have demonstrated that cell wall glycosylation and yeast-hypha morphogenesis are required for disruption of host processes that function to inactivate pathogens, leading to survival and escape of this fungal pathogen from within host phagocytes. The methods employed here are applicable to study interactions of other pathogens with phagocytic cells to dissect how specific microbial features impact different stages of phagosome maturation and the survival of the pathogen or host.
format	article
author	Judith M. Bain Johanna Louw Leanne E. Lewis Blessing Okai Catriona A. Walls Elizabeth R. Ballou Louise A. Walker Delyth Reid Carol A. Munro Alistair J. P. Brown Gordon D. Brown Neil A. R. Gow Lars P. Erwig
author_facet	Judith M. Bain Johanna Louw Leanne E. Lewis Blessing Okai Catriona A. Walls Elizabeth R. Ballou Louise A. Walker Delyth Reid Carol A. Munro Alistair J. P. Brown Gordon D. Brown Neil A. R. Gow Lars P. Erwig
author_sort	Judith M. Bain
title	<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation
title_short	<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation
title_full	<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation
title_fullStr	<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation
title_full_unstemmed	<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation
title_sort	<named-content content-type="genus-species">candida albicans</named-content> hypha formation and mannan masking of β-glucan inhibit macrophage phagosome maturation
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/330d9e9e688940309c726a225cc2763d
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<named-content content-type="genus-species">Candida albicans</named-content> Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation

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