dc.creator | Santos, Micheli Luize Barbosa | |
dc.creator | Nico, Dirlei | |
dc.creator | Oliveira, Fabrícia Alvisi de | |
dc.creator | Barreto, Aline Silva | |
dc.creator | Sousa, Iam Palatnik de | |
dc.creator | Carrillo, Eugenia | |
dc.creator | Moreno, Javier | |
dc.creator | Luca, Paula Mello de | |
dc.creator | Morrot, Alexandre | |
dc.creator | Rosa, Daniela Santoro | |
dc.creator | Palatnik, Marcos | |
dc.creator | Corrêa, Cristiane Bani | |
dc.creator | Almeida, Roque Pacheco de | |
dc.creator | Sousa, Clarisa Beatriz Palatnik de | |
dc.date | 2017-07-13T12:50:41Z | |
dc.date | 2017-07-13T12:50:41Z | |
dc.date | 2017 | |
dc.date.accessioned | 2023-09-26T20:24:48Z | |
dc.date.available | 2023-09-26T20:24:48Z | |
dc.identifier | 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. | |
dc.identifier | 1664-3224 | |
dc.identifier | https://www.arca.fiocruz.br/handle/icict/20068 | |
dc.identifier | 10.3389/fimmu.2017.00227 | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8856340 | |
dc.description | 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. | |
dc.format | application/pdf | |
dc.language | eng | |
dc.publisher | Frontiers Media | |
dc.rights | open access | |
dc.subject | Leishmaniose visceral humana | |
dc.subject | N-Glicosil Hidrolases | |
dc.subject | Epitopos de Linfócito T | |
dc.subject | Leishmania donovani | |
dc.subject | Leishmania infantum | |
dc.subject | Domínios recombinantes | |
dc.subject | Design da vacina epítopo | |
dc.subject | human visceral leishmaniasis | |
dc.subject | nucleoside hydrolase | |
dc.subject | recombinant domains | |
dc.subject | T cell epitopes | |
dc.subject | epitope vaccine design | |
dc.subject | Leishmania donovani | |
dc.subject | Leishmania infantum chagasi | |
dc.title | Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis | |
dc.type | Article | |