Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge

Candida albicans remains the fungus most frequently associated with nosocomial bloodstream infection. In disseminated candidiasis, the role of Foxp3+ regulatory T (Treg) cells remains largely unexplored. Our aims were to characterize Foxp3+ Treg-cell activation in a murine intravenous challenge mode...

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Main Authors:	Whibley, Natasha, MacCallum, Donna M, Vickers, Mark A, Zafreen, Sadia, Waldmann, Herman, Hori, Shohei, Gaffen, Sarah L, Gow, Neil A R, Barker, Robert N, Hall, Andrew M
Format:	Online
Language:	English
Published:	Wiley-VCH Verlag GmbH & Co. KGaA 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992851/

id	pubmed-3992851
recordtype	oai_dc
spelling	pubmed-39928512014-04-22 Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge Whibley, Natasha MacCallum, Donna M Vickers, Mark A Zafreen, Sadia Waldmann, Herman Hori, Shohei Gaffen, Sarah L Gow, Neil A R Barker, Robert N Hall, Andrew M Immunity to Infection Candida albicans remains the fungus most frequently associated with nosocomial bloodstream infection. In disseminated candidiasis, the role of Foxp3+ regulatory T (Treg) cells remains largely unexplored. Our aims were to characterize Foxp3+ Treg-cell activation in a murine intravenous challenge model of disseminated C. albicans infection, and determine the contribution to disease. Flow cytometric analyses demonstrated that C. albicans infection drove in vivo expansion of a splenic CD4+Foxp3+ population that correlated positively with fungal burden. Depletion from Foxp3hCD2 reporter mice in vivo confirmed that Foxp3+ cells exacerbated fungal burden and inflammatory renal disease. The CD4+Foxp3+ population expanded further after in vitro stimulation with C. albicans antigens (Ags), and included at least three cell types. These arose from proliferation of the natural Treg-cell subset, together with conversion of Foxp3− cells to the induced Treg-cell form, and to a cell type sharing effector Th17-cell characteristics, expressing ROR-γt, and secreting IL-17A. The expanded Foxp3+ T cells inhibited Th1 and Th2 responses, but enhanced Th17-cell responses to C. albicans Ags in vitro, and in vivo depletion confirmed their ability to enhance the Th17-cell response. These data lead to a model for disseminated candidiasis whereby expansion of Foxp3+ T cells promotes Th17-cell responses that drive pathology. Wiley-VCH Verlag GmbH & Co. KGaA 2014-04 2014-02-13 /pmc/articles/PMC3992851/ /pubmed/24435677 http://dx.doi.org/10.1002/eji.201343604 Text en © 2014 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Whibley, Natasha MacCallum, Donna M Vickers, Mark A Zafreen, Sadia Waldmann, Herman Hori, Shohei Gaffen, Sarah L Gow, Neil A R Barker, Robert N Hall, Andrew M
spellingShingle	Whibley, Natasha MacCallum, Donna M Vickers, Mark A Zafreen, Sadia Waldmann, Herman Hori, Shohei Gaffen, Sarah L Gow, Neil A R Barker, Robert N Hall, Andrew M Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge
author_facet	Whibley, Natasha MacCallum, Donna M Vickers, Mark A Zafreen, Sadia Waldmann, Herman Hori, Shohei Gaffen, Sarah L Gow, Neil A R Barker, Robert N Hall, Andrew M
author_sort	Whibley, Natasha
title	Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge
title_short	Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge
title_full	Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge
title_fullStr	Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge
title_full_unstemmed	Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge
title_sort	expansion of foxp3+ t-cell populations by candida albicans enhances both th17-cell responses and fungal dissemination after intravenous challenge
description	Candida albicans remains the fungus most frequently associated with nosocomial bloodstream infection. In disseminated candidiasis, the role of Foxp3+ regulatory T (Treg) cells remains largely unexplored. Our aims were to characterize Foxp3+ Treg-cell activation in a murine intravenous challenge model of disseminated C. albicans infection, and determine the contribution to disease. Flow cytometric analyses demonstrated that C. albicans infection drove in vivo expansion of a splenic CD4+Foxp3+ population that correlated positively with fungal burden. Depletion from Foxp3hCD2 reporter mice in vivo confirmed that Foxp3+ cells exacerbated fungal burden and inflammatory renal disease. The CD4+Foxp3+ population expanded further after in vitro stimulation with C. albicans antigens (Ags), and included at least three cell types. These arose from proliferation of the natural Treg-cell subset, together with conversion of Foxp3− cells to the induced Treg-cell form, and to a cell type sharing effector Th17-cell characteristics, expressing ROR-γt, and secreting IL-17A. The expanded Foxp3+ T cells inhibited Th1 and Th2 responses, but enhanced Th17-cell responses to C. albicans Ags in vitro, and in vivo depletion confirmed their ability to enhance the Th17-cell response. These data lead to a model for disseminated candidiasis whereby expansion of Foxp3+ T cells promotes Th17-cell responses that drive pathology.
publisher	Wiley-VCH Verlag GmbH & Co. KGaA
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992851/
_version_	1612080167034814464

Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge

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