| Author | Santos, Micheli Luize Barbosa | |
| Author | Nico, Dirlei | |
| Author | Oliveira, Fabrícia Alvisi de | |
| Author | Barreto, Aline Silva | |
| Author | Sousa, Iam Palatnik de | |
| Author | Carrillo, Eugenia | |
| Author | Moreno, Javier | |
| Author | Luca, Paula Mello de | |
| Author | Morrot, Alexandre | |
| Author | Rosa, Daniela Santoro | |
| Author | Palatnik, Marcos | |
| Author | Corrêa, Cristiane Bani | |
| Author | Almeida, Roque Pacheco de | |
| Author | Sousa, Clarisa Beatriz Palatnik de | |
| Access date | 2017-07-13T12:50:41Z | |
| Available date | 2017-07-13T12:50:41Z | |
| Document date | 2017 | |
| Citation | SANTOS, Micheli Luize Barbosa; et al. Leishmania donovani nucleoside hydrolase (nh36) Domains induce T-cell cytokine responses in human Visceral leishmaniasis. Frontiers in Immunology, v.8, Article 227, 19p, Mar. 2017. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/20068 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmaniose visceral humana | pt_BR |
| Subject in Portuguese | N-Glicosil Hidrolases | pt_BR |
| Subject in Portuguese | Epitopos de Linfócito T | pt_BR |
| Subject in Portuguese | Leishmania donovani | pt_BR |
| Subject in Portuguese | Leishmania infantum | pt_BR |
| Subject in Portuguese | Domínios recombinantes | pt_BR |
| Subject in Portuguese | Design da vacina epítopo | pt_BR |
| Title | Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis | pt_BR |
| Type | Article | |
| DOI | 10.3389/fimmu.2017.00227 | |
| 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. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Medicina. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Biologia e Bioquímica de Leishmania. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Medicina. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Medicina. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil. | pt_BR |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Programa de Pós-Graduação em Metrologia. Laboratório de Biometrologia. Laboratório de Biometrologia. Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | WHO Collaborating Centre for Leishmaniasis. Instituto de Salud Carlos III. Centro Nacional de Microbiologia. Madrid, Spain. | pt_BR |
| Affilliation | WHO Collaborating Centre for Leishmaniasis. Instituto de Salud Carlos III. Centro Nacional de Microbiologia. Madrid, Spain. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Laboratorio de Imunobiologia Integrada. Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina. Instituto de Investigação em Imunologia. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Vacinas Experimentais. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Vacinas Experimentais. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Hospital Clementino Fraga Filho. Laboratório de Imunohematologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Departamento de Morfologia. Aracaju, SE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Departamento de Medicina. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil / Universidade de São Paulo. Faculdade de Medicina. Instituto de Investigação em Imunologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Biologia e Bioquímica de Leishmania. Rio de Janeiro, RJ, Brasil / Universidade de São Paulo. Faculdade de Medicina. Instituto de Investigação em Imunologia. São Paulo, SP, Brasil. | pt_BR |
| Subject | human visceral leishmaniasis | pt_BR |
| Subject | nucleoside hydrolase | pt_BR |
| Subject | recombinant domains | pt_BR |
| Subject | T cell epitopes | pt_BR |
| Subject | epitope vaccine design | pt_BR |
| Subject | Leishmania donovani | pt_BR |
| Subject | Leishmania infantum chagasi | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
