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
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UnB |
Texto Completo: | 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 |
Resumo: | 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. |
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Siqueira, Isaque MedeirosWüthrich, MarcelLi, MengyiWang, HuafengLas-Casas, Lucas de OliveiraCastro, Raffael Júnio Araújo deKlein, BruceBocca, Anamélia Lorenzetti2022-06-02T11:58:40Z2022-06-02T11:58:40Z2020SIQUEIRA, 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.porreponame:Repositório Institucional da UnBinstname:Universidade de Brasília (UnB)instacron:UNBLICENSElicense.txtlicense.txttext/plain163http://repositorio2.unb.br/jspui/bitstream/10482/43881/2/license.txtba54f8d1c5f5ec8df897ad678916c701MD52open accessORIGINALARTIGO_EarlyImmuneResponse.pdfARTIGO_EarlyImmuneResponse.pdfapplication/pdf2589215http://repositorio2.unb.br/jspui/bitstream/10482/43881/1/ARTIGO_EarlyImmuneResponse.pdf3f459830936f5ad120c83c6687c809bbMD51open access10482/438812023-05-24 20:34:35.109open accessoai:repositorio2.unb.br:10482/43881U3VibWlzc8OjbyBlZmV0aXZhZGEgcG9yIGludGVncmFudGUgZGEgZXF1aXBlIGRvIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIGRhIFVuQiBkZSBhY29yZG8gY29tIGxpY2Vuw6dhIGNvbmNlZGlkYSBwZWxvIGF1dG9yIGUvb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLg==Biblioteca Digital de Teses e DissertaçõesPUBhttps://repositorio.unb.br/oai/requestopendoar:2023-05-24T23:34:35Repositório Institucional da UnB - Universidade de Brasília (UnB)false |
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 |
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 |
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 |
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_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_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 |
author |
Siqueira, Isaque Medeiros |
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 |
author_role |
author |
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 |
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.subject.keyword.pt_BR.fl_str_mv |
Doenças fúngicas Resposta imunológica Células T Inflamação Ratos - modelo animal Gânglios linfáticos |
topic |
Doenças fúngicas Resposta imunológica Células T Inflamação Ratos - modelo animal Gânglios linfáticos |
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. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2022-06-02T11:58:40Z |
dc.date.available.fl_str_mv |
2022-06-02T11:58:40Z |
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info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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. |
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https://orcid.org/ 0000-0001-6514-1793 http://orcid.org/0000-0003-3323-5300 |
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. |
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