Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis

dc.creatorSantos, Micheli Luize Barbosa
dc.creatorNico, Dirlei
dc.creatorOliveira, Fabrícia Alvisi de
dc.creatorBarreto, Aline Silva
dc.creatorSousa, Iam Palatnik de
dc.creatorCarrillo, Eugenia
dc.creatorMoreno, Javier
dc.creatorLuca, Paula Mello de
dc.creatorMorrot, Alexandre
dc.creatorRosa, Daniela Santoro
dc.creatorPalatnik, Marcos
dc.creatorCorrêa, Cristiane Bani
dc.creatorAlmeida, Roque Pacheco de
dc.creatorSousa, Clarisa Beatriz Palatnik de
dc.date2017-07-13T12:50:41Z
dc.date2017-07-13T12:50:41Z
dc.date2017
dc.date.accessioned2023-09-26T20:24:48Z
dc.date.available2023-09-26T20:24:48Z
dc.identifierSANTOS, 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.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/20068
dc.identifier10.3389/fimmu.2017.00227
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8856340
dc.descriptionDevelopment 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.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectLeishmaniose visceral humana
dc.subjectN-Glicosil Hidrolases
dc.subjectEpitopos de Linfócito T
dc.subjectLeishmania donovani
dc.subjectLeishmania infantum
dc.subjectDomínios recombinantes
dc.subjectDesign da vacina epítopo
dc.subjecthuman visceral leishmaniasis
dc.subjectnucleoside hydrolase
dc.subjectrecombinant domains
dc.subjectT cell epitopes
dc.subjectepitope vaccine design
dc.subjectLeishmania donovani
dc.subjectLeishmania infantum chagasi
dc.titleLeishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis
dc.typeArticle


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