dc.contributor.author | Barbosa Santos, Micheli Luize | |
dc.contributor.author | Nico, Dirlei | |
dc.contributor.author | de Oliveira, Fabrícia Alvisi | |
dc.contributor.author | Barreto, Aline Silva | |
dc.contributor.author | Palatnik-de-Sousa, Iam | |
dc.contributor.author | Carrillo, Eugenia | |
dc.contributor.author | Moreno, Javier | |
dc.contributor.author | de Luca, Paula Mello | |
dc.contributor.author | Morrot, Alexandre | |
dc.contributor.author | Rosa, Daniela Santoro | |
dc.contributor.author | Palatnik, Marcos | |
dc.contributor.author | Bani-Corrêa, Cristiane | |
dc.contributor.author | de Almeida, Roque Pacheco | |
dc.contributor.author | Palatnik-de-Sousa, Clarisa Beatriz | |
dc.date.accessioned | 2019-03-27T12:39:42Z | |
dc.date.available | 2019-03-27T12:39:42Z | |
dc.date.issued | 2017-03 | |
dc.identifier.citation | Front Immunol. 2017 Mar;8:227. | es_ES |
dc.identifier.issn | 1664-3224 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7408 | |
dc.description.abstract | Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-γ, IL-1β, and TNF-α and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH+ and cured subjects. F2 also promoted the highest frequencies of CD3+CD4+IL-2+TNF-α-IFN-γ-, CD3+CD4+IL-2+TNF-α+IFN-γ-, CD3+CD4+IL-2+TNF-α-IFN-γ+, and CD3+CD4+IL-2+TNF-α+IFN-γ+ T cells in cured and asymptomatic subjects. Consistent with this, the IFN-γ increase was correlated with decreased spleen (R = -0.428, P = 0.05) and liver sizes (R = -0.428, P = 0.05) and with increased hematocrit counts (R = 0.532, P = 0.015) in response to F1 domain, and with increased hematocrit (R = 0.512, P 0.02) and hemoglobin counts (R = 0.434, P = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 (R = -0.595, P = 0.005) and F2 (R = -0.462, P = 0.04). Conversely, F1 and F3 increased the CD3+CD8+IL-2+TNF-α-IFN-γ-, CD3+CD8+IL-2+TNF-α+IFN-γ-, and CD3+CD8+IL-2+TNF-α+IFN-γ+ T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4+-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8+ T-cell responses against F3 and F1, potentially involved in control of the early infection. The in silico-predicted NH36 epitopes are conserved and bind to many HL-DR and HLA and B allotypes. No human vaccine against Leishmania is available thus far. In this investigation, we identified the NH36 domains and epitopes that induce CD4+ and CD8+ T cell responses, which could be used to potentiate a human universal T-epitope vaccine against leishmaniasis. | es_ES |
dc.description.sponsorship | This work was supported by the following: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) (Fellowships 300639/2003-1 to MP, 310977/2014-2 to CP-d-S, 310797/2015-2 to AM, and grant 404400/2012-4 to CP-d-S, MP, PL, RA, JM, EC, and AM); by Fundação Carlos Chagas de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ) (grant E-26-201.583/2014, E-26-102957/2011, and E-26/111.682/2013 to CP-d-S, and fellowships E-26/102415/2010 and E-26/201747/2015 to DN); by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (grant 23038.005304/2011-0 to MS), by CNPQ-Fundação de Apoio à Pesquisa e a Inovação Tecnológica do Estado de Sergipe-PRONEX (12/2009); and by FAPITEC CNPq (PRONEX) (019.203.02712/2009-8) to RA. EC was supported by a research
contract funded via VII PN I+D+I 2013-2016 and FEDER Funds (RICET RD12/0018/0003). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Frontiers Media | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Leishmania donovani | es_ES |
dc.subject | Leishmania infantum chagasi | es_ES |
dc.subject | T cell epitopes | es_ES |
dc.subject | Epitope vaccine design | es_ES |
dc.subject | Human visceral leishmaniasis | es_ES |
dc.subject | Nucleoside hydrolase | es_ES |
dc.subject | Recombinant domains | es_ES |
dc.title | Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución- 4.0 Internacional | * |
dc.identifier.pubmedID | 28321221 | es_ES |
dc.format.volume | 8 | es_ES |
dc.format.page | 227 | es_ES |
dc.identifier.doi | 10.3389/fimmu.2017.00227 | es_ES |
dc.contributor.funder | National Council for Scientific and Technological Development (Brasil) | |
dc.contributor.funder | Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro | |
dc.contributor.funder | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil) | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.3389/fimmu.2017.00227 | es_ES |
dc.identifier.journal | Frontiers in immunology | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |