Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pntd.0008021 http://hdl.handle.net/11449/198500 |
Resumo: | Domestic dogs are the main reservoir of Leishmania infantum, a causative agent of visceral leishmaniasis (VL). The number of human disease cases is associated with the rate of canine infection. Currently available drugs are not efficient at treating canine leishmaniasis (CanL) and months after the treatment most dogs show disease relapse, therefore the development of new drugs or new therapeutic strategies should be sought. In CanL, dogs lack the ability to mount a specific cellular immune response suitable for combating the parasite and manipulation of cytokine signaling pathway has the potential to form part of effective immunotherapeutic methods. In this study, recombinant canine cytokines (rcaIL-12, rcaIL-2, rcaIL-15 and rcaIL-7) and soluble receptor IL-10R1 (rcasIL-10R1), with antagonistic activity, were evaluated for the first time in combination (rcaIL-12/rcaIL-2, rcaIL-12/rcaIL-15, rcaIL-12/rcasIL-10R1, rcaIL-15/rcaIL-7) or alone (rcasIL-10R1) to evaluate their immunomodula-tory capacity in peripheral blood mononuclear cells (PBMCs) from dogs with leishmaniasis. All the combinations of recombinant proteins tested were shown to improve lymphoprolifera-tive response. Further, the combinations rcaIL-12/rcaIL-2 and rcaIL-12/rcaIL-15 promoted a decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and rcaIL-12/rcasIL-10R1 induced IFN-γ and TNF-α production in PBMCs. Furthermore, the combination IL-12/IL-15 led to an increased in T-bet expression in lymphocytes. These findings are encouraging and indicate the use of rcaIL-12 and rcaIL-15 in future in vivo studies aimed at achieving polarization of cellular immune responses in dogs with leishmaniasis, which may contribute to the development of an effective treatment against CanL. |
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Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasisDomestic dogs are the main reservoir of Leishmania infantum, a causative agent of visceral leishmaniasis (VL). The number of human disease cases is associated with the rate of canine infection. Currently available drugs are not efficient at treating canine leishmaniasis (CanL) and months after the treatment most dogs show disease relapse, therefore the development of new drugs or new therapeutic strategies should be sought. In CanL, dogs lack the ability to mount a specific cellular immune response suitable for combating the parasite and manipulation of cytokine signaling pathway has the potential to form part of effective immunotherapeutic methods. In this study, recombinant canine cytokines (rcaIL-12, rcaIL-2, rcaIL-15 and rcaIL-7) and soluble receptor IL-10R1 (rcasIL-10R1), with antagonistic activity, were evaluated for the first time in combination (rcaIL-12/rcaIL-2, rcaIL-12/rcaIL-15, rcaIL-12/rcasIL-10R1, rcaIL-15/rcaIL-7) or alone (rcasIL-10R1) to evaluate their immunomodula-tory capacity in peripheral blood mononuclear cells (PBMCs) from dogs with leishmaniasis. All the combinations of recombinant proteins tested were shown to improve lymphoprolifera-tive response. Further, the combinations rcaIL-12/rcaIL-2 and rcaIL-12/rcaIL-15 promoted a decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and rcaIL-12/rcasIL-10R1 induced IFN-γ and TNF-α production in PBMCs. Furthermore, the combination IL-12/IL-15 led to an increased in T-bet expression in lymphocytes. These findings are encouraging and indicate the use of rcaIL-12 and rcaIL-15 in future in vivo studies aimed at achieving polarization of cellular immune responses in dogs with leishmaniasis, which may contribute to the development of an effective treatment against CanL.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Animal Clinic Surgery and Animal Reproduction São Paulo State University (UNESP) School of Veterinary MedicineOswaldo Cruz Foundation Gonçalo Moniz Research Center Laboratory of Structural and Molecular Pathology (LAPEM), Rua Waldemar Falcão, CandealDepartment of Animal Clinic Surgery and Animal Reproduction São Paulo State University (UNESP) School of Veterinary MedicineCAPES: 001FAPESP: 2017/ 10906-8CNPq: 400063/2016-6CNPq: 400913/2013-5CNPq: 573839/2008-5Universidade Estadual Paulista (Unesp)Laboratory of Structural and Molecular Pathology (LAPEM)Costa, Sidnei Ferro [UNESP]Gomes, Vinícius Oliveira [UNESP]Maciel, Marilene Oliveira Dos Santos [UNESP]Melo, Larissa Martins [UNESP]Venturin, Gabriela Lovizutto [UNESP]Bragato, Jaqueline Poleto [UNESP]Rebech, Gabriela Torres [UNESP]Santos, Catiule de Oliveirade Oliveira, Bárbara Maria Nascimentode Sá Oliveira, Geraldo Gilenode Lima, Valéria Marçal Felix [UNESP]2020-12-12T01:14:35Z2020-12-12T01:14:35Z2020-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-21http://dx.doi.org/10.1371/journal.pntd.0008021PLoS Neglected Tropical Diseases, v. 14, n. 1, p. 1-21, 2020.1935-27351935-2727http://hdl.handle.net/11449/19850010.1371/journal.pntd.00080212-s2.0-85079204063Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLoS Neglected Tropical Diseasesinfo:eu-repo/semantics/openAccess2021-10-22T13:12:46Zoai:repositorio.unesp.br:11449/198500Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:49:09.615721Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
title |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
spellingShingle |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis Costa, Sidnei Ferro [UNESP] |
title_short |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
title_full |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
title_fullStr |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
title_full_unstemmed |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
title_sort |
Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis |
author |
Costa, Sidnei Ferro [UNESP] |
author_facet |
Costa, Sidnei Ferro [UNESP] Gomes, Vinícius Oliveira [UNESP] Maciel, Marilene Oliveira Dos Santos [UNESP] Melo, Larissa Martins [UNESP] Venturin, Gabriela Lovizutto [UNESP] Bragato, Jaqueline Poleto [UNESP] Rebech, Gabriela Torres [UNESP] Santos, Catiule de Oliveira de Oliveira, Bárbara Maria Nascimento de Sá Oliveira, Geraldo Gileno de Lima, Valéria Marçal Felix [UNESP] |
author_role |
author |
author2 |
Gomes, Vinícius Oliveira [UNESP] Maciel, Marilene Oliveira Dos Santos [UNESP] Melo, Larissa Martins [UNESP] Venturin, Gabriela Lovizutto [UNESP] Bragato, Jaqueline Poleto [UNESP] Rebech, Gabriela Torres [UNESP] Santos, Catiule de Oliveira de Oliveira, Bárbara Maria Nascimento de Sá Oliveira, Geraldo Gileno de Lima, Valéria Marçal Felix [UNESP] |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Laboratory of Structural and Molecular Pathology (LAPEM) |
dc.contributor.author.fl_str_mv |
Costa, Sidnei Ferro [UNESP] Gomes, Vinícius Oliveira [UNESP] Maciel, Marilene Oliveira Dos Santos [UNESP] Melo, Larissa Martins [UNESP] Venturin, Gabriela Lovizutto [UNESP] Bragato, Jaqueline Poleto [UNESP] Rebech, Gabriela Torres [UNESP] Santos, Catiule de Oliveira de Oliveira, Bárbara Maria Nascimento de Sá Oliveira, Geraldo Gileno de Lima, Valéria Marçal Felix [UNESP] |
description |
Domestic dogs are the main reservoir of Leishmania infantum, a causative agent of visceral leishmaniasis (VL). The number of human disease cases is associated with the rate of canine infection. Currently available drugs are not efficient at treating canine leishmaniasis (CanL) and months after the treatment most dogs show disease relapse, therefore the development of new drugs or new therapeutic strategies should be sought. In CanL, dogs lack the ability to mount a specific cellular immune response suitable for combating the parasite and manipulation of cytokine signaling pathway has the potential to form part of effective immunotherapeutic methods. In this study, recombinant canine cytokines (rcaIL-12, rcaIL-2, rcaIL-15 and rcaIL-7) and soluble receptor IL-10R1 (rcasIL-10R1), with antagonistic activity, were evaluated for the first time in combination (rcaIL-12/rcaIL-2, rcaIL-12/rcaIL-15, rcaIL-12/rcasIL-10R1, rcaIL-15/rcaIL-7) or alone (rcasIL-10R1) to evaluate their immunomodula-tory capacity in peripheral blood mononuclear cells (PBMCs) from dogs with leishmaniasis. All the combinations of recombinant proteins tested were shown to improve lymphoprolifera-tive response. Further, the combinations rcaIL-12/rcaIL-2 and rcaIL-12/rcaIL-15 promoted a decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and rcaIL-12/rcasIL-10R1 induced IFN-γ and TNF-α production in PBMCs. Furthermore, the combination IL-12/IL-15 led to an increased in T-bet expression in lymphocytes. These findings are encouraging and indicate the use of rcaIL-12 and rcaIL-15 in future in vivo studies aimed at achieving polarization of cellular immune responses in dogs with leishmaniasis, which may contribute to the development of an effective treatment against CanL. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T01:14:35Z 2020-12-12T01:14:35Z 2020-01-01 |
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/10.1371/journal.pntd.0008021 PLoS Neglected Tropical Diseases, v. 14, n. 1, p. 1-21, 2020. 1935-2735 1935-2727 http://hdl.handle.net/11449/198500 10.1371/journal.pntd.0008021 2-s2.0-85079204063 |
url |
http://dx.doi.org/10.1371/journal.pntd.0008021 http://hdl.handle.net/11449/198500 |
identifier_str_mv |
PLoS Neglected Tropical Diseases, v. 14, n. 1, p. 1-21, 2020. 1935-2735 1935-2727 10.1371/journal.pntd.0008021 2-s2.0-85079204063 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS Neglected Tropical Diseases |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1-21 |
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 |
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Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129361018093568 |