Combined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis

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dc.contributor.authorCosta, Sidnei Ferro [UNESP]
dc.contributor.authorGomes, Vinícius Oliveira [UNESP]
dc.contributor.authorMaciel, Marilene Oliveira Dos Santos [UNESP]
dc.contributor.authorMelo, Larissa Martins [UNESP]
dc.contributor.authorVenturin, Gabriela Lovizutto [UNESP]
dc.contributor.authorBragato, Jaqueline Poleto [UNESP]
dc.contributor.authorRebech, Gabriela Torres [UNESP]
dc.contributor.authorSantos, Catiule de Oliveira
dc.contributor.authorde Oliveira, Bárbara Maria Nascimento
dc.contributor.authorde Sá Oliveira, Geraldo Gileno
dc.contributor.authorde Lima, Valéria Marçal Felix [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionLaboratory of Structural and Molecular Pathology (LAPEM)
dc.date.accessioned2020-12-12T01:14:35Z
dc.date.available2020-12-12T01:14:35Z
dc.date.issued2020-01-01
dc.description.abstractDomestic 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.en
dc.description.affiliationDepartment of Animal Clinic Surgery and Animal Reproduction São Paulo State University (UNESP) School of Veterinary Medicine
dc.description.affiliationOswaldo Cruz Foundation Gonçalo Moniz Research Center Laboratory of Structural and Molecular Pathology (LAPEM), Rua Waldemar Falcão, Candeal
dc.description.affiliationUnespDepartment of Animal Clinic Surgery and Animal Reproduction São Paulo State University (UNESP) School of Veterinary Medicine
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCAPES: 001
dc.description.sponsorshipIdFAPESP: 2017/ 10906-8
dc.description.sponsorshipIdCNPq: 400063/2016-6
dc.description.sponsorshipIdCNPq: 400913/2013-5
dc.description.sponsorshipIdCNPq: 573839/2008-5
dc.format.extent1-21
dc.identifierhttp://dx.doi.org/10.1371/journal.pntd.0008021
dc.identifier.citationPLoS Neglected Tropical Diseases, v. 14, n. 1, p. 1-21, 2020.
dc.identifier.doi10.1371/journal.pntd.0008021
dc.identifier.issn1935-2735
dc.identifier.issn1935-2727
dc.identifier.scopus2-s2.0-85079204063
dc.identifier.urihttp://hdl.handle.net/11449/198500
dc.language.isoeng
dc.relation.ispartofPLoS Neglected Tropical Diseases
dc.sourceScopus
dc.titleCombined in vitro il-12 and il-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasisen
dc.typeArtigo

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