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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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Detalles Bibliográficos
Autores principales: Li, Chao, Meng, Yang, Li, Hailong, Du, Wei, Gao, Xindi, Suo, Chenhao, Gao, Yiru, Ni, Yue, Sun, Tianshu, Yang, Sheng, Lan, Tian, Xin, Meiling, Ding, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431737/
https://www.ncbi.nlm.nih.gov/pubmed/37526401
http://dx.doi.org/10.1080/22221751.2023.2244087
Descripción
Sumario: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.