Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling

ABSTRACT Organisms must adapt to changes in oxygen tension if they are to exploit the energetic benefits of reducing oxygen while minimizing the potentially damaging effects of oxidation. Consequently, organisms in all eukaryotic kingdoms display robust adaptation to hypoxia (low oxygen levels). Thi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Arnab Pradhan, Gabriela M. Avelar, Judith M. Bain, Delma S. Childers, Daniel E. Larcombe, Mihai G. Netea, Elena Shekhova, Carol A. Munro, Gordon D. Brown, Lars P. Erwig, Neil A. R. Gow, Alistair J. P. Brown
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	hypoxia Candida albicans cell wall β-glucan masking mitochondrial signaling cAMP-protein kinase A signaling Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7246d978081d4c2eaaefcf2803e7a1d6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7246d978081d4c2eaaefcf2803e7a1d6
record_format	dspace
spelling	oai:doaj.org-article:7246d978081d4c2eaaefcf2803e7a1d62021-11-15T15:52:19ZHypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling10.1128/mBio.01318-182150-7511https://doaj.org/article/7246d978081d4c2eaaefcf2803e7a1d62018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01318-18https://doaj.org/toc/2150-7511ABSTRACT Organisms must adapt to changes in oxygen tension if they are to exploit the energetic benefits of reducing oxygen while minimizing the potentially damaging effects of oxidation. Consequently, organisms in all eukaryotic kingdoms display robust adaptation to hypoxia (low oxygen levels). This is particularly important for fungal pathogens that colonize hypoxic niches in the host. We show that adaptation to hypoxia in the major fungal pathogen of humans Candida albicans includes changes in cell wall structure and reduced exposure, at the cell surface, of β-glucan, a key pathogen-associated molecular pattern (PAMP). This leads to reduced phagocytosis by murine bone marrow-derived macrophages and decreased production of IL-10, RANTES, and TNF-α by peripheral blood mononuclear cells, suggesting that hypoxia-induced β-glucan masking has a significant effect upon C. albicans-host interactions. We show that hypoxia-induced β-glucan masking is dependent upon both mitochondrial and cAMP-protein kinase A (PKA) signaling. The decrease in β-glucan exposure is blocked by mutations that affect mitochondrial functionality (goa1Δ and upc2Δ) or that decrease production of hydrogen peroxide in the inner membrane space (sod1Δ). Furthermore, β-glucan masking is enhanced by mutations that elevate mitochondrial reactive oxygen species (aox1Δ). The β-glucan masking defects displayed by goa1Δ and upc2Δ cells are suppressed by exogenous dibutyryl-cAMP. Also, mutations that inactivate cAMP synthesis (cyr1Δ) or PKA (tpk1Δ tpk2Δ) block the masking phenotype. Our data suggest that C. albicans responds to hypoxic niches by inducing β-glucan masking via a mitochondrial cAMP-PKA signaling pathway, thereby modulating local immune responses and promoting fungal colonization. IMPORTANCE Animal, plant, and fungal cells occupy environments that impose changes in oxygen tension. Consequently, many species have evolved mechanisms that permit robust adaptation to these changes. The fungal pathogen Candida albicans can colonize hypoxic (low oxygen) niches in its human host, such as the lower gastrointestinal tract and inflamed tissues, but to colonize its host, the fungus must also evade local immune defenses. We reveal, for the first time, a defined link between hypoxic adaptation and immune evasion in C. albicans. As this pathogen adapts to hypoxia, it undergoes changes in cell wall structure that include masking of β-glucan at its cell surface, and it becomes better able to evade phagocytosis by innate immune cells. We also define the signaling mechanisms that mediate hypoxia-induced β-glucan masking, showing that they are dependent on mitochondrial signaling and the cAMP-protein kinase pathway. Therefore, hypoxia appears to trigger immune evasion in this fungal pathogen.Arnab PradhanGabriela M. AvelarJudith M. BainDelma S. ChildersDaniel E. LarcombeMihai G. NeteaElena ShekhovaCarol A. MunroGordon D. BrownLars P. ErwigNeil A. R. GowAlistair J. P. BrownAmerican Society for MicrobiologyarticlehypoxiaCandida albicanscell wallβ-glucan maskingmitochondrial signalingcAMP-protein kinase A signalingMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia Candida albicans cell wall β-glucan masking mitochondrial signaling cAMP-protein kinase A signaling Microbiology QR1-502
spellingShingle	hypoxia Candida albicans cell wall β-glucan masking mitochondrial signaling cAMP-protein kinase A signaling Microbiology QR1-502 Arnab Pradhan Gabriela M. Avelar Judith M. Bain Delma S. Childers Daniel E. Larcombe Mihai G. Netea Elena Shekhova Carol A. Munro Gordon D. Brown Lars P. Erwig Neil A. R. Gow Alistair J. P. Brown Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling
description	ABSTRACT Organisms must adapt to changes in oxygen tension if they are to exploit the energetic benefits of reducing oxygen while minimizing the potentially damaging effects of oxidation. Consequently, organisms in all eukaryotic kingdoms display robust adaptation to hypoxia (low oxygen levels). This is particularly important for fungal pathogens that colonize hypoxic niches in the host. We show that adaptation to hypoxia in the major fungal pathogen of humans Candida albicans includes changes in cell wall structure and reduced exposure, at the cell surface, of β-glucan, a key pathogen-associated molecular pattern (PAMP). This leads to reduced phagocytosis by murine bone marrow-derived macrophages and decreased production of IL-10, RANTES, and TNF-α by peripheral blood mononuclear cells, suggesting that hypoxia-induced β-glucan masking has a significant effect upon C. albicans-host interactions. We show that hypoxia-induced β-glucan masking is dependent upon both mitochondrial and cAMP-protein kinase A (PKA) signaling. The decrease in β-glucan exposure is blocked by mutations that affect mitochondrial functionality (goa1Δ and upc2Δ) or that decrease production of hydrogen peroxide in the inner membrane space (sod1Δ). Furthermore, β-glucan masking is enhanced by mutations that elevate mitochondrial reactive oxygen species (aox1Δ). The β-glucan masking defects displayed by goa1Δ and upc2Δ cells are suppressed by exogenous dibutyryl-cAMP. Also, mutations that inactivate cAMP synthesis (cyr1Δ) or PKA (tpk1Δ tpk2Δ) block the masking phenotype. Our data suggest that C. albicans responds to hypoxic niches by inducing β-glucan masking via a mitochondrial cAMP-PKA signaling pathway, thereby modulating local immune responses and promoting fungal colonization. IMPORTANCE Animal, plant, and fungal cells occupy environments that impose changes in oxygen tension. Consequently, many species have evolved mechanisms that permit robust adaptation to these changes. The fungal pathogen Candida albicans can colonize hypoxic (low oxygen) niches in its human host, such as the lower gastrointestinal tract and inflamed tissues, but to colonize its host, the fungus must also evade local immune defenses. We reveal, for the first time, a defined link between hypoxic adaptation and immune evasion in C. albicans. As this pathogen adapts to hypoxia, it undergoes changes in cell wall structure that include masking of β-glucan at its cell surface, and it becomes better able to evade phagocytosis by innate immune cells. We also define the signaling mechanisms that mediate hypoxia-induced β-glucan masking, showing that they are dependent on mitochondrial signaling and the cAMP-protein kinase pathway. Therefore, hypoxia appears to trigger immune evasion in this fungal pathogen.
format	article
author	Arnab Pradhan Gabriela M. Avelar Judith M. Bain Delma S. Childers Daniel E. Larcombe Mihai G. Netea Elena Shekhova Carol A. Munro Gordon D. Brown Lars P. Erwig Neil A. R. Gow Alistair J. P. Brown
author_facet	Arnab Pradhan Gabriela M. Avelar Judith M. Bain Delma S. Childers Daniel E. Larcombe Mihai G. Netea Elena Shekhova Carol A. Munro Gordon D. Brown Lars P. Erwig Neil A. R. Gow Alistair J. P. Brown
author_sort	Arnab Pradhan
title	Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling
title_short	Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling
title_full	Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling
title_fullStr	Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling
title_full_unstemmed	Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling
title_sort	hypoxia promotes immune evasion by triggering β-glucan masking on the <named-content content-type="genus-species">candida albicans</named-content> cell surface via mitochondrial and camp-protein kinase a signaling
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/7246d978081d4c2eaaefcf2803e7a1d6
work_keys_str_mv	AT arnabpradhan hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT gabrielamavelar hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT judithmbain hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT delmaschilders hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT danielelarcombe hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT mihaignetea hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT elenashekhova hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT carolamunro hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT gordondbrown hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT larsperwig hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT neilargow hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling AT alistairjpbrown hypoxiapromotesimmuneevasionbytriggeringbglucanmaskingonthenamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentcellsurfaceviamitochondrialandcampproteinkinaseasignaling
_version_	1718427281621254144

Hypoxia Promotes Immune Evasion by Triggering β-Glucan Masking on the <named-content content-type="genus-species">Candida albicans</named-content> Cell Surface via Mitochondrial and cAMP-Protein Kinase A Signaling

Ejemplares similares