Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis

Detalhes bibliográficos
Autor(a) principal: Fraga-Silva, Thais Fernanda de Campos [UNESP]
Data de Publicação: 2022
Outros Autores: Munhoz-Alves, Natália [UNESP], Mimura, Luiza Ayumi Nishiyama [UNESP], Oliveira, Larissa Ragozo Cardoso de [UNESP], Figueiredo-Godoi, Lívia Mara Alves [UNESP], Garcia, Maíra Terra [UNESP], Oliveira, Evelyn Silva [UNESP], Ishikawa, Larissa Lumi Watanabe [UNESP], Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP], Bonato, Vânia Luiza Deperon, Junqueira, Juliana Campos [UNESP], Bagagli, Eduardo [UNESP], Sartori, Alexandrina [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/jof8040386
http://hdl.handle.net/11449/241646
Resumo: Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.
id UNSP_e05bd417e89e58429b53fb6fb6b3cda2
oai_identifier_str oai:repositorio.unesp.br:11449/241646
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosiscentral nervous systemexperimental autoimmune encephalomyelitisGalleria mellonellamicroglianon-albicans Candida sppCandidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Chemistry and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)Postgraduate Program in Tropical Disease Botucatu Medical School São Paulo State University (UNESP)Institute of Science and Technology São Paulo State University (UNESP)Department of Biochemistry and Immunology Ribeirao Preto Medical School University of Sao Paulo (USP)Department of Chemistry and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)Postgraduate Program in Tropical Disease Botucatu Medical School São Paulo State University (UNESP)Institute of Science and Technology São Paulo State University (UNESP)CNPq: 146779/2018-5CNPq: 152790/2016-0FAPESP: 2019/11213-1CNPq: 307269/2017-5Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Fraga-Silva, Thais Fernanda de Campos [UNESP]Munhoz-Alves, Natália [UNESP]Mimura, Luiza Ayumi Nishiyama [UNESP]Oliveira, Larissa Ragozo Cardoso de [UNESP]Figueiredo-Godoi, Lívia Mara Alves [UNESP]Garcia, Maíra Terra [UNESP]Oliveira, Evelyn Silva [UNESP]Ishikawa, Larissa Lumi Watanabe [UNESP]Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]Bonato, Vânia Luiza DeperonJunqueira, Juliana Campos [UNESP]Bagagli, Eduardo [UNESP]Sartori, Alexandrina [UNESP]2023-03-01T21:14:39Z2023-03-01T21:14:39Z2022-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/jof8040386Journal of Fungi, v. 8, n. 4, 2022.2309-608Xhttp://hdl.handle.net/11449/24164610.3390/jof80403862-s2.0-85129058389Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Fungiinfo:eu-repo/semantics/openAccess2023-03-01T21:14:40Zoai:repositorio.unesp.br:11449/241646Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:14:15.976256Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
title Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
spellingShingle Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
Fraga-Silva, Thais Fernanda de Campos [UNESP]
central nervous system
experimental autoimmune encephalomyelitis
Galleria mellonella
microglia
non-albicans Candida spp
title_short Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
title_full Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
title_fullStr Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
title_full_unstemmed Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
title_sort Systemic Infection by Non-albicans Candida Species Affects the Development of a Murine Model of Multiple Sclerosis
author Fraga-Silva, Thais Fernanda de Campos [UNESP]
author_facet Fraga-Silva, Thais Fernanda de Campos [UNESP]
Munhoz-Alves, Natália [UNESP]
Mimura, Luiza Ayumi Nishiyama [UNESP]
Oliveira, Larissa Ragozo Cardoso de [UNESP]
Figueiredo-Godoi, Lívia Mara Alves [UNESP]
Garcia, Maíra Terra [UNESP]
Oliveira, Evelyn Silva [UNESP]
Ishikawa, Larissa Lumi Watanabe [UNESP]
Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Bonato, Vânia Luiza Deperon
Junqueira, Juliana Campos [UNESP]
Bagagli, Eduardo [UNESP]
Sartori, Alexandrina [UNESP]
author_role author
author2 Munhoz-Alves, Natália [UNESP]
Mimura, Luiza Ayumi Nishiyama [UNESP]
Oliveira, Larissa Ragozo Cardoso de [UNESP]
Figueiredo-Godoi, Lívia Mara Alves [UNESP]
Garcia, Maíra Terra [UNESP]
Oliveira, Evelyn Silva [UNESP]
Ishikawa, Larissa Lumi Watanabe [UNESP]
Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Bonato, Vânia Luiza Deperon
Junqueira, Juliana Campos [UNESP]
Bagagli, Eduardo [UNESP]
Sartori, Alexandrina [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Fraga-Silva, Thais Fernanda de Campos [UNESP]
Munhoz-Alves, Natália [UNESP]
Mimura, Luiza Ayumi Nishiyama [UNESP]
Oliveira, Larissa Ragozo Cardoso de [UNESP]
Figueiredo-Godoi, Lívia Mara Alves [UNESP]
Garcia, Maíra Terra [UNESP]
Oliveira, Evelyn Silva [UNESP]
Ishikawa, Larissa Lumi Watanabe [UNESP]
Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]
Bonato, Vânia Luiza Deperon
Junqueira, Juliana Campos [UNESP]
Bagagli, Eduardo [UNESP]
Sartori, Alexandrina [UNESP]
dc.subject.por.fl_str_mv central nervous system
experimental autoimmune encephalomyelitis
Galleria mellonella
microglia
non-albicans Candida spp
topic central nervous system
experimental autoimmune encephalomyelitis
Galleria mellonella
microglia
non-albicans Candida spp
description Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-01
2023-03-01T21:14:39Z
2023-03-01T21:14:39Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3390/jof8040386
Journal of Fungi, v. 8, n. 4, 2022.
2309-608X
http://hdl.handle.net/11449/241646
10.3390/jof8040386
2-s2.0-85129058389
url http://dx.doi.org/10.3390/jof8040386
http://hdl.handle.net/11449/241646
identifier_str_mv Journal of Fungi, v. 8, n. 4, 2022.
2309-608X
10.3390/jof8040386
2-s2.0-85129058389
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Fungi
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808129039393619968