Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis
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| Autor principal: | |
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| Fecha de Publicación: | 2020 |
| Otros Autores: | , , , , , , |
| Formato: | Article |
| Lenguaje: | por |
| Fuente: | Repositório Institucional da UnB |
| Download full: | https://repositorio.unb.br/handle/10482/43881 https://doi.org/10.1371/journal.pntd.0008386 https://orcid.org/ 0000-0001-6514-1793 http://orcid.org/0000-0003-3323-5300 |
Sumario: | Chromoblastomycosis (CBM) is a chronic worldwide subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. It is difficult to treat patients with the disease, mainly because of its recalcitrant nature. The correct activation of host immune response is critical to avoid fungal persistence in the tissue and disease chronification. CD4+ T cells are crucial for the development of protective immunity to F. pedrosoi infection. Here, we investigated T helper cell response dynamics during experimental CBM. Following footpad injection with F. pedrosoi hyphae and conidia, T cells were skewed towards a Th17 and Th1 phenotype. The Th17 population was the main Th cell subset found in the infected area during the early stages of experimental murine CBM, followed by Th1 predominance in the later stages, coinciding with the remission phase of the disease in this experimental model. Depletion of CD25+ cells, which leads to a reduction of Treg cells in the draining lymph node, resulted in decline in fungal burden after 14 days of infection. However, fungal cells were not cleared in the later stages of the disease, prolonging CBM clinical features in those animals. IL-17A and IFN-γ neutralization hindered fungal cell elimination in the course of the disease. Similarly, in dectin-2 KO animals, Th17 contraction in the course of experimental CBM was accompanied by fungal burden decrease in the first 14 days of infection, although it did not affect disease resolution. In this study, we gained insight into T helper subsets’ dynamics following footpad injections of F. pedrosoi propagules and uncovered their contribution to disease resolution. The Th17 population proved to be important in eliminating fungal cells in the early stages of infection. The Th1 population, in turn, closely assisted by Treg cells, proved to be relevant not only in the elimination of fungal cells at the beginning of infection but also essential for their complete elimination in later stages of the disease in a mouse experimental model of CBM. |
| _version_ | 1871442262355869696 |
|---|---|
| author | Siqueira, Isaque Medeiros |
| author2 | Wüthrich, Marcel Li, Mengyi Wang, Huafeng Las-Casas, Lucas de Oliveira Castro, Raffael Júnio Araújo de Klein, Bruce Bocca, Anamélia Lorenzetti |
| author2_role | author author author author author author author |
| author_browse | Bocca, Anamélia Lorenzetti Castro, Raffael Júnio Araújo de Klein, Bruce Las-Casas, Lucas de Oliveira Li, Mengyi Siqueira, Isaque Medeiros Wang, Huafeng Wüthrich, Marcel |
| author_facet | Siqueira, Isaque Medeiros Wüthrich, Marcel Li, Mengyi Wang, Huafeng Las-Casas, Lucas de Oliveira Castro, Raffael Júnio Araújo de Klein, Bruce Bocca, Anamélia Lorenzetti |
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| collection | Repositório Institucional da UnB |
| dc.contributor.affiliation.pt_BR.fl_str_mv | University of Brasília, School of Medicine, Molecular Pathology Post-Graduate Program University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Wisconsin, United States of America University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Wisconsin, United States of America University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Wisconsin, United States of America University of Brasília, School of Medicine, Molecular Pathology Post-Graduate Program University of Brasília, School of Medicine, Molecular Pathology Post-Graduate Program University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Department of Internal Medicine, Department of Medical Microbiology and Immunology University of Brasília, Institute of Biological Sciences, Department of Cell Biology |
| dc.contributor.author.fl_str_mv | Siqueira, Isaque Medeiros Wüthrich, Marcel Li, Mengyi Wang, Huafeng Las-Casas, Lucas de Oliveira Castro, Raffael Júnio Araújo de Klein, Bruce Bocca, Anamélia Lorenzetti |
| dc.date.accessioned.fl_str_mv | 2022-06-02T11:58:40Z |
| dc.date.available.fl_str_mv | 2022-06-02T11:58:40Z |
| dc.date.issued.fl_str_mv | 2020 |
| dc.identifier.citation.fl_str_mv | SIQUEIRA, Isaque Medeiros et al. Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis. PLOS Neglected Tropical Diseases, v. 14, n. 6, e0008386, 2020. DOI: https://doi.org/10.1371/journal.pntd.0008386. Disponível em: https://journals.plos.org/plosntds/article/authors?id=10.1371/journal.pntd.0008386. Acesso em: 2 jun. 2022. |
| dc.identifier.doi.pt_BR.fl_str_mv | https://doi.org/10.1371/journal.pntd.0008386 |
| dc.identifier.orcid.pt_BR.fl_str_mv | https://orcid.org/ 0000-0001-6514-1793 http://orcid.org/0000-0003-3323-5300 |
| dc.identifier.uri.fl_str_mv | https://repositorio.unb.br/handle/10482/43881 |
| dc.language.iso.fl_str_mv | por |
| dc.publisher.none.fl_str_mv | PLOS |
| dc.rights.driver.fl_str_mv | (CC0) info:eu-repo/semantics/openAccess |
| dc.source.none.fl_str_mv | reponame:Repositório Institucional da UnB instname:Universidade de Brasília (UnB) instacron:UNB |
| dc.subject.keyword.pt_BR.fl_str_mv | Doenças fúngicas Resposta imunológica Células T Inflamação Ratos - modelo animal Gânglios linfáticos |
| dc.title.pt_BR.fl_str_mv | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| dc.type.driver.fl_str_mv | info:eu-repo/semantics/article |
| dc.type.status.fl_str_mv | info:eu-repo/semantics/publishedVersion |
| description | Chromoblastomycosis (CBM) is a chronic worldwide subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. It is difficult to treat patients with the disease, mainly because of its recalcitrant nature. The correct activation of host immune response is critical to avoid fungal persistence in the tissue and disease chronification. CD4+ T cells are crucial for the development of protective immunity to F. pedrosoi infection. Here, we investigated T helper cell response dynamics during experimental CBM. Following footpad injection with F. pedrosoi hyphae and conidia, T cells were skewed towards a Th17 and Th1 phenotype. The Th17 population was the main Th cell subset found in the infected area during the early stages of experimental murine CBM, followed by Th1 predominance in the later stages, coinciding with the remission phase of the disease in this experimental model. Depletion of CD25+ cells, which leads to a reduction of Treg cells in the draining lymph node, resulted in decline in fungal burden after 14 days of infection. However, fungal cells were not cleared in the later stages of the disease, prolonging CBM clinical features in those animals. IL-17A and IFN-γ neutralization hindered fungal cell elimination in the course of the disease. Similarly, in dectin-2 KO animals, Th17 contraction in the course of experimental CBM was accompanied by fungal burden decrease in the first 14 days of infection, although it did not affect disease resolution. In this study, we gained insight into T helper subsets’ dynamics following footpad injections of F. pedrosoi propagules and uncovered their contribution to disease resolution. The Th17 population proved to be important in eliminating fungal cells in the early stages of infection. The Th1 population, in turn, closely assisted by Treg cells, proved to be relevant not only in the elimination of fungal cells at the beginning of infection but also essential for their complete elimination in later stages of the disease in a mouse experimental model of CBM. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | UNB_2e4eaa2e2643a731a87c4415e87f8fc3 |
| identifier_str_mv | SIQUEIRA, Isaque Medeiros et al. Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis. PLOS Neglected Tropical Diseases, v. 14, n. 6, e0008386, 2020. DOI: https://doi.org/10.1371/journal.pntd.0008386. Disponível em: https://journals.plos.org/plosntds/article/authors?id=10.1371/journal.pntd.0008386. Acesso em: 2 jun. 2022. |
| instacron_str | UNB |
| institution | UNB |
| instname_str | Universidade de Brasília (UnB) |
| language | por |
| network_acronym_str | UNB |
| network_name_str | Repositório Institucional da UnB |
| oai_identifier_str | oai:repositorio.unb.br:10482/43881 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher.none.fl_str_mv | PLOS |
| reponame_str | Repositório Institucional da UnB |
| repository.mail.fl_str_mv | repositorio@unb.br |
| repository.name.fl_str_mv | Repositório Institucional da UnB - Universidade de Brasília (UnB) |
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| spelling | Siqueira, Isaque MedeirosWüthrich, MarcelLi, MengyiWang, HuafengLas-Casas, Lucas de OliveiraCastro, Raffael Júnio Araújo deKlein, BruceBocca, Anamélia LorenzettiUniversity of Brasília, School of Medicine, Molecular Pathology Post-Graduate ProgramUniversity of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Wisconsin, United States of AmericaUniversity of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Wisconsin, United States of AmericaUniversity of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Wisconsin, United States of AmericaUniversity of Brasília, School of Medicine, Molecular Pathology Post-Graduate ProgramUniversity of Brasília, School of Medicine, Molecular Pathology Post-Graduate ProgramUniversity of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Department of Internal Medicine, Department of Medical Microbiology and ImmunologyUniversity of Brasília, Institute of Biological Sciences, Department of Cell Biology2022-06-02T11:58:40Z2022-06-02T11:58:40Z2020SIQUEIRA, Isaque Medeiros et al. Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis. PLOS Neglected Tropical Diseases, v. 14, n. 6, e0008386, 2020. DOI: https://doi.org/10.1371/journal.pntd.0008386. Disponível em: https://journals.plos.org/plosntds/article/authors?id=10.1371/journal.pntd.0008386. Acesso em: 2 jun. 2022.https://repositorio.unb.br/handle/10482/43881https://doi.org/10.1371/journal.pntd.0008386https://orcid.org/ 0000-0001-6514-1793http://orcid.org/0000-0003-3323-5300PLOS(CC0)info:eu-repo/semantics/openAccessEarly immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDoenças fúngicasResposta imunológicaCélulas TInflamaçãoRatos - modelo animalGânglios linfáticosChromoblastomycosis (CBM) is a chronic worldwide subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. It is difficult to treat patients with the disease, mainly because of its recalcitrant nature. The correct activation of host immune response is critical to avoid fungal persistence in the tissue and disease chronification. CD4+ T cells are crucial for the development of protective immunity to F. pedrosoi infection. Here, we investigated T helper cell response dynamics during experimental CBM. Following footpad injection with F. pedrosoi hyphae and conidia, T cells were skewed towards a Th17 and Th1 phenotype. The Th17 population was the main Th cell subset found in the infected area during the early stages of experimental murine CBM, followed by Th1 predominance in the later stages, coinciding with the remission phase of the disease in this experimental model. Depletion of CD25+ cells, which leads to a reduction of Treg cells in the draining lymph node, resulted in decline in fungal burden after 14 days of infection. However, fungal cells were not cleared in the later stages of the disease, prolonging CBM clinical features in those animals. IL-17A and IFN-γ neutralization hindered fungal cell elimination in the course of the disease. Similarly, in dectin-2 KO animals, Th17 contraction in the course of experimental CBM was accompanied by fungal burden decrease in the first 14 days of infection, although it did not affect disease resolution. In this study, we gained insight into T helper subsets’ dynamics following footpad injections of F. pedrosoi propagules and uncovered their contribution to disease resolution. The Th17 population proved to be important in eliminating fungal cells in the early stages of infection. The Th1 population, in turn, closely assisted by Treg cells, proved to be relevant not only in the elimination of fungal cells at the beginning of infection but also essential for their complete elimination in later stages of the disease in a mouse experimental model of CBM.Instituto de Ciências Biológicas (IB)Departamento de Biologia Celular (IB CEL)Faculdade de Medicina (FM)Programa de Pós-Graduação em Patologia Molecularporreponame:Repositório Institucional da UnBinstname:Universidade de Brasília (UnB)instacron:UNBLICENSElicense.txtlicense.txttext/plain163http://repositorio.unb.br/bitstream/10482/43881/2/license.txtba54f8d1c5f5ec8df897ad678916c701MD52open accessORIGINALARTIGO_EarlyImmuneResponse.pdfARTIGO_EarlyImmuneResponse.pdfapplication/pdf2589215http://repositorio.unb.br/bitstream/10482/43881/1/ARTIGO_EarlyImmuneResponse.pdf3f459830936f5ad120c83c6687c809bbMD51open access10482/438812025-03-25 17:10:17.874open accessoai:repositorio.unb.br:10482/43881U3VibWlzc8OjbyBlZmV0aXZhZGEgcG9yIGludGVncmFudGUgZGEgZXF1aXBlIGRvIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIGRhIFVuQiBkZSBhY29yZG8gY29tIGxpY2Vuw6dhIGNvbmNlZGlkYSBwZWxvIGF1dG9yIGUvb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLg==Repositório InstitucionalPUBhttps://repositorio.unb.br/oai/requestrepositorio@unb.bropendoar:2025-03-25T20:10:17Repositório Institucional da UnB - Universidade de Brasília (UnB) |
| spellingShingle | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis Siqueira, Isaque Medeiros Doenças fúngicas Resposta imunológica Células T Inflamação Ratos - modelo animal Gânglios linfáticos |
| status_str | publishedVersion |
| title | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| title_full | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| title_fullStr | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| title_full_unstemmed | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| title_short | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| title_sort | Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis |
| topic | Doenças fúngicas Resposta imunológica Células T Inflamação Ratos - modelo animal Gânglios linfáticos |
| url | https://repositorio.unb.br/handle/10482/43881 https://doi.org/10.1371/journal.pntd.0008386 https://orcid.org/ 0000-0001-6514-1793 http://orcid.org/0000-0003-3323-5300 |