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Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection

Cryptococcus neoformans is a major etiological agent of fungal meningoencephalitis. The outcome of cryptococcosis depends on the complex interactions between the pathogenic fungus and host immunity. The understanding of how C. neoformans manipulates the host immune response through its pathogenic fa...

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Autores principales: Yang, Ya-li, Fan, Yi-bin, Gao, Lei, Zhang, Chao, Gu, Ju-lin, Pan, Wei-hua, Fang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201341/
https://www.ncbi.nlm.nih.gov/pubmed/35720283
http://dx.doi.org/10.3389/fimmu.2022.890258
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author Yang, Ya-li
Fan, Yi-bin
Gao, Lei
Zhang, Chao
Gu, Ju-lin
Pan, Wei-hua
Fang, Wei
author_facet Yang, Ya-li
Fan, Yi-bin
Gao, Lei
Zhang, Chao
Gu, Ju-lin
Pan, Wei-hua
Fang, Wei
author_sort Yang, Ya-li
collection PubMed
description Cryptococcus neoformans is a major etiological agent of fungal meningoencephalitis. The outcome of cryptococcosis depends on the complex interactions between the pathogenic fungus and host immunity. The understanding of how C. neoformans manipulates the host immune response through its pathogenic factors remains incomplete. In this study, we defined the roles of a previously uncharacterized protein, Csn1201, in cryptococcal fitness and host immunity. Use of both inhalational and intravenous mouse models demonstrated that the CSN1201 deletion significantly blocked the pulmonary infection and extrapulmonary dissemination of C. neoformans. The in vivo hypovirulent phenotype of the csn1201Δ mutant was attributed to a combination of multiple factors, including preferential dendritic cell accumulation, enhanced Th1 and Th17 immune responses, decreased intracellular survival inside macrophages, and attenuated blood–brain barrier transcytosis rather than exclusively to pathogenic fitness. The csn1201Δ mutant exhibited decreased tolerance to various stressors in vitro, along with reduced capsule production and enhanced cell wall thickness under host-relevant conditions, indicating that the CSN1201 deletion might promote the exposure of cell wall components and thus induce a protective immune response. Taken together, our results strongly support the importance of cryptococcal Csn1201 in pulmonary immune responses and disseminated infection.
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spelling pubmed-92013412022-06-17 Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection Yang, Ya-li Fan, Yi-bin Gao, Lei Zhang, Chao Gu, Ju-lin Pan, Wei-hua Fang, Wei Front Immunol Immunology Cryptococcus neoformans is a major etiological agent of fungal meningoencephalitis. The outcome of cryptococcosis depends on the complex interactions between the pathogenic fungus and host immunity. The understanding of how C. neoformans manipulates the host immune response through its pathogenic factors remains incomplete. In this study, we defined the roles of a previously uncharacterized protein, Csn1201, in cryptococcal fitness and host immunity. Use of both inhalational and intravenous mouse models demonstrated that the CSN1201 deletion significantly blocked the pulmonary infection and extrapulmonary dissemination of C. neoformans. The in vivo hypovirulent phenotype of the csn1201Δ mutant was attributed to a combination of multiple factors, including preferential dendritic cell accumulation, enhanced Th1 and Th17 immune responses, decreased intracellular survival inside macrophages, and attenuated blood–brain barrier transcytosis rather than exclusively to pathogenic fitness. The csn1201Δ mutant exhibited decreased tolerance to various stressors in vitro, along with reduced capsule production and enhanced cell wall thickness under host-relevant conditions, indicating that the CSN1201 deletion might promote the exposure of cell wall components and thus induce a protective immune response. Taken together, our results strongly support the importance of cryptococcal Csn1201 in pulmonary immune responses and disseminated infection. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201341/ /pubmed/35720283 http://dx.doi.org/10.3389/fimmu.2022.890258 Text en Copyright © 2022 Yang, Fan, Gao, Zhang, Gu, Pan and Fang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yang, Ya-li
Fan, Yi-bin
Gao, Lei
Zhang, Chao
Gu, Ju-lin
Pan, Wei-hua
Fang, Wei
Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection
title Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection
title_full Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection
title_fullStr Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection
title_full_unstemmed Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection
title_short Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated Infection
title_sort cryptococcus neoformans csn1201 is associated with pulmonary immune responses and disseminated infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201341/
https://www.ncbi.nlm.nih.gov/pubmed/35720283
http://dx.doi.org/10.3389/fimmu.2022.890258
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