<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production

ABSTRACT The interaction of Candida albicans with macrophages induces the production of interleukin 1β (IL-1β) through inflammasome activation in a process that is required for host survival. C. albicans hypha formation has been linked to IL-1β production, but the question of whether hyphae are suff...

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Autores principales:	Melanie Wellington, Kristy Koselny, Damian J. Krysan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/edfd31080ece4f62b665304589a00c42
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spelling	oai:doaj.org-article:edfd31080ece4f62b665304589a00c422021-11-15T15:40:24Z<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production10.1128/mBio.00433-122150-7511https://doaj.org/article/edfd31080ece4f62b665304589a00c422013-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00433-12https://doaj.org/toc/2150-7511ABSTRACT The interaction of Candida albicans with macrophages induces the production of interleukin 1β (IL-1β) through inflammasome activation in a process that is required for host survival. C. albicans hypha formation has been linked to IL-1β production, but the question of whether hyphae are sufficient to trigger IL-1β production has not been examined directly. To address this question, a C. albicans library of 165 transcription factor deletion mutants was screened for strains with altered IL-1β production by lipopolysaccharide (LPS)-primed J774 cells, a murine macrophage-like cell line. Eight mutants with decreased and two mutants with increased IL-1β secretion were identified. In addition, 12 mutants with previously identified morphology deficits were found to induce IL-1β secretion to levels similar to those of the wild type. Examination of the morphology of both low and normal IL-1β-inducing mutants in macrophages revealed that two mutants (upc2Δ/upc2Δ and ahr1Δ/Δ mutants) were indistinguishable from the wild type with respect to morphology yet induced low levels of IL-1β; conversely, the ndt80Δ/Δ mutant was deficient for hypha formation but induced levels of IL-1β similar to those of the wild type. Transcription factor mutants deficient for IL-1β secretion also caused markedly lower levels of macrophage lysis. Similarly, the ability of a mutant to cause macrophage lysis was independent of its ability to form hyphae. Taken together, our observations indicate that the physical formation of hyphae is not sufficient to trigger IL-1β secretion or macrophage lysis and suggest that other mechanisms, such as pyroptosis, a caspase-1-dependent response to intracellular pathogens, may play a role in the interaction of macrophages with C. albicans. IMPORTANCE The ability of Candida albicans to transition from yeast to filamentous cells plays an important and complex role in pathogenesis. Recent results from a number of investigators indicate that the host responds to yeast and hyphal C. albicans differently. For example, a C. albicans mutant unable to form hyphae also fails to induce interleukin 1β (IL-1β) secretion from macrophages. We have identified C. albicans transcription factor mutants that have decreased IL-1β secretion but retain the ability to form hyphae in response to macrophages. In addition, these mutants cause significantly less macrophage lysis. These observations indicate that the physical presence of the hyphal structure in the macrophage is not sufficient to trigger IL-1β secretion nor does it cause physical lysis of the cell. Our data indicate that characteristics of hyphae separate from its physical morphology are responsible for triggering the release of IL-1β release and causing macrophage lysis. Since these observations are inconsistent with some current models, alternative mechanisms for the interaction of C. albicans with macrophages must be considered.Melanie WellingtonKristy KoselnyDamian J. KrysanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 1 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Melanie Wellington Kristy Koselny Damian J. Krysan <named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
description	ABSTRACT The interaction of Candida albicans with macrophages induces the production of interleukin 1β (IL-1β) through inflammasome activation in a process that is required for host survival. C. albicans hypha formation has been linked to IL-1β production, but the question of whether hyphae are sufficient to trigger IL-1β production has not been examined directly. To address this question, a C. albicans library of 165 transcription factor deletion mutants was screened for strains with altered IL-1β production by lipopolysaccharide (LPS)-primed J774 cells, a murine macrophage-like cell line. Eight mutants with decreased and two mutants with increased IL-1β secretion were identified. In addition, 12 mutants with previously identified morphology deficits were found to induce IL-1β secretion to levels similar to those of the wild type. Examination of the morphology of both low and normal IL-1β-inducing mutants in macrophages revealed that two mutants (upc2Δ/upc2Δ and ahr1Δ/Δ mutants) were indistinguishable from the wild type with respect to morphology yet induced low levels of IL-1β; conversely, the ndt80Δ/Δ mutant was deficient for hypha formation but induced levels of IL-1β similar to those of the wild type. Transcription factor mutants deficient for IL-1β secretion also caused markedly lower levels of macrophage lysis. Similarly, the ability of a mutant to cause macrophage lysis was independent of its ability to form hyphae. Taken together, our observations indicate that the physical formation of hyphae is not sufficient to trigger IL-1β secretion or macrophage lysis and suggest that other mechanisms, such as pyroptosis, a caspase-1-dependent response to intracellular pathogens, may play a role in the interaction of macrophages with C. albicans. IMPORTANCE The ability of Candida albicans to transition from yeast to filamentous cells plays an important and complex role in pathogenesis. Recent results from a number of investigators indicate that the host responds to yeast and hyphal C. albicans differently. For example, a C. albicans mutant unable to form hyphae also fails to induce interleukin 1β (IL-1β) secretion from macrophages. We have identified C. albicans transcription factor mutants that have decreased IL-1β secretion but retain the ability to form hyphae in response to macrophages. In addition, these mutants cause significantly less macrophage lysis. These observations indicate that the physical presence of the hyphal structure in the macrophage is not sufficient to trigger IL-1β secretion nor does it cause physical lysis of the cell. Our data indicate that characteristics of hyphae separate from its physical morphology are responsible for triggering the release of IL-1β release and causing macrophage lysis. Since these observations are inconsistent with some current models, alternative mechanisms for the interaction of C. albicans with macrophages must be considered.
format	article
author	Melanie Wellington Kristy Koselny Damian J. Krysan
author_facet	Melanie Wellington Kristy Koselny Damian J. Krysan
author_sort	Melanie Wellington
title	<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
title_short	<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
title_full	<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
title_fullStr	<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
title_full_unstemmed	<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production
title_sort	<named-content content-type="genus-species">candida albicans</named-content> morphogenesis is not required for macrophage interleukin 1β production
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/edfd31080ece4f62b665304589a00c42
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<named-content content-type="genus-species">Candida albicans</named-content> Morphogenesis Is Not Required for Macrophage Interleukin 1β Production

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