<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses

ABSTRACT Infectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate that Cryptococcus neoformans signals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101, C....

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Autores principales:	Teresa R. O'Meara, Stephanie M. Holmer, Kyla Selvig, Fred Dietrich, J. Andrew Alspaugh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/408e1de071ce42da9374cbe488073c4c
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spelling	oai:doaj.org-article:408e1de071ce42da9374cbe488073c4c2021-11-15T15:40:23Z<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses10.1128/mBio.00522-122150-7511https://doaj.org/article/408e1de071ce42da9374cbe488073c4c2013-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00522-12https://doaj.org/toc/2150-7511ABSTRACT Infectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate that Cryptococcus neoformans signals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101, C. neoformans exhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. This host immune response to the rim101Δ mutant strain is characterized by increased neutrophil influx into the infected lungs and an altered pattern of host cytokine expression compared to the response to wild-type cryptococcal infection. To identify genes associated with the observed phenotypes, we performed whole-genome RNA sequencing experiments under capsule-inducing conditions. We defined the downstream regulon of the Rim101 transcription factor and determined potential cell wall processes involved in the capsule attachment defects and altered mechanisms of virulence in the rim101Δ mutant. The cell wall generates structural stability for the cell and allows the attachment of surface molecules such as capsule polysaccharides. In turn, the capsule provides an effective mask for the immunogenic cell wall, shielding it from recognition by the host immune system. IMPORTANCE Cryptococcus neoformans is an opportunistic human pathogen that is a significant cause of death in immunocompromised individuals. There are two major causes of death due to this pathogen: meningitis due to uncontrolled fungal proliferation in the brain in the face of a weakened immune system and immune reconstitution inflammatory syndrome characterized by an overactive immune response to subclinical levels of the pathogen. In this study, we examined how C. neoformans uses the conserved Rim101 transcription factor to specifically remodel the host-pathogen interface, thus regulating the host immune response. These studies explored the complex ways in which successful microbial pathogens induce phenotypes that ensure their own survival while simultaneously controlling the nature and degree of the associated host response.Teresa R. O'MearaStephanie M. HolmerKyla SelvigFred DietrichJ. Andrew AlspaughAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 1 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Teresa R. O'Meara Stephanie M. Holmer Kyla Selvig Fred Dietrich J. Andrew Alspaugh <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
description	ABSTRACT Infectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate that Cryptococcus neoformans signals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101, C. neoformans exhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. This host immune response to the rim101Δ mutant strain is characterized by increased neutrophil influx into the infected lungs and an altered pattern of host cytokine expression compared to the response to wild-type cryptococcal infection. To identify genes associated with the observed phenotypes, we performed whole-genome RNA sequencing experiments under capsule-inducing conditions. We defined the downstream regulon of the Rim101 transcription factor and determined potential cell wall processes involved in the capsule attachment defects and altered mechanisms of virulence in the rim101Δ mutant. The cell wall generates structural stability for the cell and allows the attachment of surface molecules such as capsule polysaccharides. In turn, the capsule provides an effective mask for the immunogenic cell wall, shielding it from recognition by the host immune system. IMPORTANCE Cryptococcus neoformans is an opportunistic human pathogen that is a significant cause of death in immunocompromised individuals. There are two major causes of death due to this pathogen: meningitis due to uncontrolled fungal proliferation in the brain in the face of a weakened immune system and immune reconstitution inflammatory syndrome characterized by an overactive immune response to subclinical levels of the pathogen. In this study, we examined how C. neoformans uses the conserved Rim101 transcription factor to specifically remodel the host-pathogen interface, thus regulating the host immune response. These studies explored the complex ways in which successful microbial pathogens induce phenotypes that ensure their own survival while simultaneously controlling the nature and degree of the associated host response.
format	article
author	Teresa R. O'Meara Stephanie M. Holmer Kyla Selvig Fred Dietrich J. Andrew Alspaugh
author_facet	Teresa R. O'Meara Stephanie M. Holmer Kyla Selvig Fred Dietrich J. Andrew Alspaugh
author_sort	Teresa R. O'Meara
title	<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
title_short	<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
title_full	<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
title_fullStr	<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
title_full_unstemmed	<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
title_sort	<named-content content-type="genus-species">cryptococcus neoformans</named-content> rim101 is associated with cell wall remodeling and evasion of the host immune responses
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/408e1de071ce42da9374cbe488073c4c
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<named-content content-type="genus-species">Cryptococcus neoformans</named-content> Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses

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