X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection

Abstract Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral res...

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Autores principales:	Israel Diniz-Lima, Pablo Rodrigo da Rosa, Elias Barbosa da Silva-Junior, Joyce Cristina Guimarães-de-Oliveira, Elisangela Oliveira de Freitas, Danielle de Oliveira Nascimento, Alexandre Morrot, Leonardo Nimrichter, Jose Osvaldo Previato, Lucia Mendonça-Previato, Leonardo Freire-de-Lima, Debora Decote-Ricardo, Celio Geraldo Freire-de-Lima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04abe7e76106492ca660dae9f8631235
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spelling	oai:doaj.org-article:04abe7e76106492ca660dae9f86312352021-12-02T18:02:22ZX-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection10.1038/s41598-021-97041-92045-2322https://doaj.org/article/04abe7e76106492ca660dae9f86312352021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97041-9https://doaj.org/toc/2045-2322Abstract Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.Israel Diniz-LimaPablo Rodrigo da RosaElias Barbosa da Silva-JuniorJoyce Cristina Guimarães-de-OliveiraElisangela Oliveira de FreitasDanielle de Oliveira NascimentoAlexandre MorrotLeonardo NimrichterJose Osvaldo PreviatoLucia Mendonça-PreviatoLeonardo Freire-de-LimaDebora Decote-RicardoCelio Geraldo Freire-de-LimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Israel Diniz-Lima Pablo Rodrigo da Rosa Elias Barbosa da Silva-Junior Joyce Cristina Guimarães-de-Oliveira Elisangela Oliveira de Freitas Danielle de Oliveira Nascimento Alexandre Morrot Leonardo Nimrichter Jose Osvaldo Previato Lucia Mendonça-Previato Leonardo Freire-de-Lima Debora Decote-Ricardo Celio Geraldo Freire-de-Lima X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
description	Abstract Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.
format	article
author	Israel Diniz-Lima Pablo Rodrigo da Rosa Elias Barbosa da Silva-Junior Joyce Cristina Guimarães-de-Oliveira Elisangela Oliveira de Freitas Danielle de Oliveira Nascimento Alexandre Morrot Leonardo Nimrichter Jose Osvaldo Previato Lucia Mendonça-Previato Leonardo Freire-de-Lima Debora Decote-Ricardo Celio Geraldo Freire-de-Lima
author_facet	Israel Diniz-Lima Pablo Rodrigo da Rosa Elias Barbosa da Silva-Junior Joyce Cristina Guimarães-de-Oliveira Elisangela Oliveira de Freitas Danielle de Oliveira Nascimento Alexandre Morrot Leonardo Nimrichter Jose Osvaldo Previato Lucia Mendonça-Previato Leonardo Freire-de-Lima Debora Decote-Ricardo Celio Geraldo Freire-de-Lima
author_sort	Israel Diniz-Lima
title	X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
title_short	X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
title_full	X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
title_fullStr	X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
title_full_unstemmed	X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
title_sort	x-linked immunodeficient (xid) mice exhibit high susceptibility to cryptococcus gattii infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/04abe7e76106492ca660dae9f8631235
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X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection

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