Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fcimb.2022.1084526 http://hdl.handle.net/11449/248434 |
Resumo: | Introduction: Regulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus Sporothrix spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known. Methods: We evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti-Sporothrix vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration. Results: Tregs depletion enhanced the frequency of specific IFNγ+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with S. brasiliensis in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting. Discussion: Our results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti-Sporothrix vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against Sporothrix spp. |
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Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix sppDEREG miceenolaseregulatory T cellsSporothrix schenckiisporotrichosisvaccineIntroduction: Regulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus Sporothrix spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known. Methods: We evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti-Sporothrix vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration. Results: Tregs depletion enhanced the frequency of specific IFNγ+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with S. brasiliensis in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting. Discussion: Our results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti-Sporothrix vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against Sporothrix spp.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP), SPDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP), SPUniversidade Estadual Paulista (UNESP)Batista-Duharte, Alexander [UNESP]Téllez-Martínez, Damiana [UNESP]Portuondo, Deivys Leandro [UNESP]Carlos, Iracilda Zeppone [UNESP]2023-07-29T13:44:00Z2023-07-29T13:44:00Z2023-02-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fcimb.2022.1084526Frontiers in Cellular and Infection Microbiology, v. 12.2235-2988http://hdl.handle.net/11449/24843410.3389/fcimb.2022.10845262-s2.0-85149051913Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Cellular and Infection Microbiologyinfo:eu-repo/semantics/openAccess2024-06-21T15:19:31Zoai:repositorio.unesp.br:11449/248434Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-06-21T15:19:31Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
title |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
spellingShingle |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp Batista-Duharte, Alexander [UNESP] DEREG mice enolase regulatory T cells Sporothrix schenckii sporotrichosis vaccine |
title_short |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
title_full |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
title_fullStr |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
title_full_unstemmed |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
title_sort |
Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp |
author |
Batista-Duharte, Alexander [UNESP] |
author_facet |
Batista-Duharte, Alexander [UNESP] Téllez-Martínez, Damiana [UNESP] Portuondo, Deivys Leandro [UNESP] Carlos, Iracilda Zeppone [UNESP] |
author_role |
author |
author2 |
Téllez-Martínez, Damiana [UNESP] Portuondo, Deivys Leandro [UNESP] Carlos, Iracilda Zeppone [UNESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Batista-Duharte, Alexander [UNESP] Téllez-Martínez, Damiana [UNESP] Portuondo, Deivys Leandro [UNESP] Carlos, Iracilda Zeppone [UNESP] |
dc.subject.por.fl_str_mv |
DEREG mice enolase regulatory T cells Sporothrix schenckii sporotrichosis vaccine |
topic |
DEREG mice enolase regulatory T cells Sporothrix schenckii sporotrichosis vaccine |
description |
Introduction: Regulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus Sporothrix spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known. Methods: We evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti-Sporothrix vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration. Results: Tregs depletion enhanced the frequency of specific IFNγ+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with S. brasiliensis in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting. Discussion: Our results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti-Sporothrix vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against Sporothrix spp. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T13:44:00Z 2023-07-29T13:44:00Z 2023-02-10 |
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/10.3389/fcimb.2022.1084526 Frontiers in Cellular and Infection Microbiology, v. 12. 2235-2988 http://hdl.handle.net/11449/248434 10.3389/fcimb.2022.1084526 2-s2.0-85149051913 |
url |
http://dx.doi.org/10.3389/fcimb.2022.1084526 http://hdl.handle.net/11449/248434 |
identifier_str_mv |
Frontiers in Cellular and Infection Microbiology, v. 12. 2235-2988 10.3389/fcimb.2022.1084526 2-s2.0-85149051913 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Cellular and Infection Microbiology |
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_ |
1803650220012077056 |