A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model

ABSTRACT Cryptococcus neoformans is a fungal pathogen that infects the lungs and then often disseminates to the central nervous system, causing meningitis. How Cryptococcus is able to suppress host immunity and escape the antifungal activity of macrophages remains incompletely understood. We reporte...

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Autores principales:	Yina Wang, Keyi Wang, Jorge A. Masso-Silva, Amariliz Rivera, Chaoyang Xue
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Cryptococcus neoformans Fbp1 fungal vaccine invasive fungal infection mice Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c7e0ea029bd64dbebccbe4fc2141fa52
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spelling	oai:doaj.org-article:c7e0ea029bd64dbebccbe4fc2141fa522021-11-15T15:54:45ZA Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model10.1128/mBio.02145-192150-7511https://doaj.org/article/c7e0ea029bd64dbebccbe4fc2141fa522019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02145-19https://doaj.org/toc/2150-7511ABSTRACT Cryptococcus neoformans is a fungal pathogen that infects the lungs and then often disseminates to the central nervous system, causing meningitis. How Cryptococcus is able to suppress host immunity and escape the antifungal activity of macrophages remains incompletely understood. We reported that the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase, promotes Cryptococcus virulence by regulating host-Cryptococcus interactions. Our recent studies demonstrated that the fbp1Δ mutant elicited superior protective Th1 host immunity in the lungs and that the enhanced immunogenicity of heat-killed fbp1Δ yeast cells can be harnessed to confer protection against a subsequent infection with the virulent parental strain. We therefore examined the use of heat-killed fbp1Δ cells in several vaccination strategies. Interestingly, the vaccine protection remains effective even in mice depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that vaccinating mice with heat-killed fbp1Δ induces significant cross-protection against challenge with diverse invasive fungal pathogens, including C. neoformans, C. gattii, and Aspergillus fumigatus, as well as partial protection against Candida albicans. Thus, our data suggest that the heat-killed fbp1Δ strain has the potential to be a suitable vaccine candidate against cryptococcosis and other invasive fungal infections in both immunocompetent and immunocompromised populations. IMPORTANCE Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity. Here, we demonstrate that the heat-killed fbp1Δ cells (HK-fbp1) can be harnessed to confer protection against a challenge by the virulent parental strain, even in animals depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that HK-fbp1 vaccination induces significant cross-protection against challenge with diverse invasive fungal pathogens. Thus, our data suggest that HK-fbp1 has the potential to be a broad-spectrum vaccine candidate against invasive fungal infections in both immunocompetent and immunocompromised populations.Yina WangKeyi WangJorge A. Masso-SilvaAmariliz RiveraChaoyang XueAmerican Society for MicrobiologyarticleCryptococcus neoformansFbp1fungal vaccineinvasive fungal infectionmiceMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cryptococcus neoformans Fbp1 fungal vaccine invasive fungal infection mice Microbiology QR1-502
spellingShingle	Cryptococcus neoformans Fbp1 fungal vaccine invasive fungal infection mice Microbiology QR1-502 Yina Wang Keyi Wang Jorge A. Masso-Silva Amariliz Rivera Chaoyang Xue A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
description	ABSTRACT Cryptococcus neoformans is a fungal pathogen that infects the lungs and then often disseminates to the central nervous system, causing meningitis. How Cryptococcus is able to suppress host immunity and escape the antifungal activity of macrophages remains incompletely understood. We reported that the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase, promotes Cryptococcus virulence by regulating host-Cryptococcus interactions. Our recent studies demonstrated that the fbp1Δ mutant elicited superior protective Th1 host immunity in the lungs and that the enhanced immunogenicity of heat-killed fbp1Δ yeast cells can be harnessed to confer protection against a subsequent infection with the virulent parental strain. We therefore examined the use of heat-killed fbp1Δ cells in several vaccination strategies. Interestingly, the vaccine protection remains effective even in mice depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that vaccinating mice with heat-killed fbp1Δ induces significant cross-protection against challenge with diverse invasive fungal pathogens, including C. neoformans, C. gattii, and Aspergillus fumigatus, as well as partial protection against Candida albicans. Thus, our data suggest that the heat-killed fbp1Δ strain has the potential to be a suitable vaccine candidate against cryptococcosis and other invasive fungal infections in both immunocompetent and immunocompromised populations. IMPORTANCE Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity. Here, we demonstrate that the heat-killed fbp1Δ cells (HK-fbp1) can be harnessed to confer protection against a challenge by the virulent parental strain, even in animals depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that HK-fbp1 vaccination induces significant cross-protection against challenge with diverse invasive fungal pathogens. Thus, our data suggest that HK-fbp1 has the potential to be a broad-spectrum vaccine candidate against invasive fungal infections in both immunocompetent and immunocompromised populations.
format	article
author	Yina Wang Keyi Wang Jorge A. Masso-Silva Amariliz Rivera Chaoyang Xue
author_facet	Yina Wang Keyi Wang Jorge A. Masso-Silva Amariliz Rivera Chaoyang Xue
author_sort	Yina Wang
title	A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
title_short	A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
title_full	A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
title_fullStr	A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
title_full_unstemmed	A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
title_sort	heat-killed <italic toggle="yes">cryptococcus</italic> mutant strain induces host protection against multiple invasive mycoses in a murine vaccine model
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/c7e0ea029bd64dbebccbe4fc2141fa52
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A Heat-Killed <italic toggle="yes">Cryptococcus</italic> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model

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