Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection

Systemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel r...

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Main Authors: Chao Li, Yang Meng, Hailong Li, Wei Du, Xindi Gao, Chenhao Suo, Yiru Gao, Yue Ni, Tianshu Sun, Sheng Yang, Tian Lan, Meiling Xin, Chen Ding
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2244087
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author Chao Li
Yang Meng
Hailong Li
Wei Du
Xindi Gao
Chenhao Suo
Yiru Gao
Yue Ni
Tianshu Sun
Sheng Yang
Tian Lan
Meiling Xin
Chen Ding
author_facet Chao Li
Yang Meng
Hailong Li
Wei Du
Xindi Gao
Chenhao Suo
Yiru Gao
Yue Ni
Tianshu Sun
Sheng Yang
Tian Lan
Meiling Xin
Chen Ding
author_sort Chao Li
collection DOAJ
description Systemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of C. neoformans virulence. C. neoformans prm1Δ cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, prm1Δ cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed prm1Δ cells was found to facilitate the host immunological defence against infection with wild-type C. neoformans. Further investigation demonstrated that prm1Δ cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that C. neoformans Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.
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institution Kabale University
issn 2222-1751
language English
publishDate 2023-12-01
publisher Taylor & Francis Group
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series Emerging Microbes and Infections
spelling doaj-art-fa073cd5159f48aca583e04047ebee632025-08-20T03:31:10ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2244087Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infectionChao Li0Yang Meng1Hailong Li2Wei Du3Xindi Gao4Chenhao Suo5Yiru Gao6Yue Ni7Tianshu Sun8Sheng Yang9Tian Lan10Meiling Xin11Chen Ding12College of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaNHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaBeijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, People’s Republic of ChinaSystemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of C. neoformans virulence. C. neoformans prm1Δ cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, prm1Δ cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed prm1Δ cells was found to facilitate the host immunological defence against infection with wild-type C. neoformans. Further investigation demonstrated that prm1Δ cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that C. neoformans Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.https://www.tandfonline.com/doi/10.1080/22221751.2023.2244087Cryptococcus neoformansPrm1cell wallfungal vaccineIFN-γmacrophage polarization
spellingShingle Chao Li
Yang Meng
Hailong Li
Wei Du
Xindi Gao
Chenhao Suo
Yiru Gao
Yue Ni
Tianshu Sun
Sheng Yang
Tian Lan
Meiling Xin
Chen Ding
Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection
Emerging Microbes and Infections
Cryptococcus neoformans
Prm1
cell wall
fungal vaccine
IFN-γ
macrophage polarization
title Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection
title_full Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection
title_fullStr Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection
title_full_unstemmed Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection
title_short Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection
title_sort immunization with a heat killed prm1 deletion strain protects the host from cryptococcus neoformans infection
topic Cryptococcus neoformans
Prm1
cell wall
fungal vaccine
IFN-γ
macrophage polarization
url https://www.tandfonline.com/doi/10.1080/22221751.2023.2244087
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