Leishmania donovani nucleoside hydrolase (NH36) Domains induce T-cell cytokine responses in human Visceral leishmaniasis

dc.citation.volume8
dc.contributor.authorBarbosa Santos, Micheli Luize
dc.contributor.authorNico, Dirlei
dc.contributor.authorde Oliveira, Fabricia Alvisi
dc.contributor.authorBarreto, Aline Silva
dc.contributor.authorPalatnik-de-Sousa, Iam
dc.contributor.authorCarrillo, Eugenia [UNIFESP]
dc.contributor.authorMoreno, Javier
dc.contributor.authorde Luca, Paula Mello
dc.contributor.authorMorrot, Alexandre
dc.contributor.authorRosa, Daniela Santoro [UNIFESP]
dc.contributor.authorPalatnik, Marcos
dc.contributor.authorBani-Correa, Cristiane
dc.contributor.authorde Almeida, Roque Pacheco
dc.contributor.authorPalatnik-de-Sousa, Clarisa Beatriz
dc.coverageLausanne
dc.date.accessioned2020-07-17T14:02:40Z
dc.date.available2020-07-17T14:02:40Z
dc.date.issued2017
dc.description.abstractDevelopment 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-gamma, IL-1 beta, and TNF-a 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-alpha-IFN-gamma(-), CD3(+)CD4(+)IL-2(+)TNF-alpha+IFN-gamma(-), CD3(+)CD4(+)IL-2(+)TNF-alpha-IFN-gamma(+), and CD3(+)CD4(+)IL-2(+)TNF-alpha+IFN-gamma(+) T cells in cured and asymptomatic subjects. Consistent with this, the IFN-gamma 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-alpha-IFN-gamma(-), CD3(+)CD8(+)IL-2(+)TNF-alpha+IFN-gamma(-), and CD3(+)CD8(+)IL-2(+)TNF-alpha+IFN-gamma(+) 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.en
dc.description.affiliationUniv Fed Sergipe HU UFS, Dept Med, Univ Hosp, Mol Biol Lab, Aracaju, Sergipe, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Microbiol Geral, Lab Biol Bioquim Leishmania, Rio De Janeiro, RJ, Brazil
dc.description.affiliationPontificia Univ Catolica Rio de Janeiro, Lab Biometrol, Programa Posgrad Metrol, Rio De Janeiro, RJ, Brazil
dc.description.affiliationInst Salud Carlos III, WHO Collaborating Ctr Leishmaniasis, Ctr Nacl Microbiol, Madrid, Comunidad De Ma, Spain
dc.description.affiliationInst Oswaldo Cruz, Lab Imunoparasitol, Rio De Janeiro, RJ, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Microbiologia Paulo de Goes, Dept Imunol, Lab Imunol Integrada, Rio De Janeiro, RJ, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Inst Invest Imunol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Vacinas Expt, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Fac Med, Lab Imunohematol, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, RJ, Brazil
dc.description.affiliationUniv Fed Sergipe HU UFS, Dept Morfol, Aracaju, Sergipe, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Vacinas Expt, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)
dc.description.sponsorshipFundacao Carlos Chagas de Amparo a Pesquisa do Estado de Rio de Janeiro (FAPERJ)
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior
dc.description.sponsorshipCNPQ-Fundacao de Apoio a Pesquisa e a Inovacao Tecnologica do Estado de Sergipe-PRONEX
dc.description.sponsorshipFAPITEC CNPq (PRONEX)
dc.description.sponsorshipVII PN I+D+I
dc.description.sponsorshipFEDER Funds
dc.description.sponsorshipIDCNPq: 300639/2003-1
dc.description.sponsorshipIDCNPq: 310977/2014-2
dc.description.sponsorshipIDCNPq: 310797/2015-2
dc.description.sponsorshipIDCNPq: 404400/2012-4
dc.description.sponsorshipIDFAPERJ: E-26-201.583/2014
dc.description.sponsorshipIDFAPERJ: E-26-102957/2011
dc.description.sponsorshipIDFAPERJ: E-26/111.682/2013
dc.description.sponsorshipIDFAPERJ: E-26/102415/2010
dc.description.sponsorshipIDFAPERJ: E-26/201747/2015
dc.description.sponsorshipIDCAPES: 23038.005304/2011-0
dc.description.sponsorshipIDCNPQ-PRONEX: 12/2009
dc.description.sponsorshipIDFAPITEC CNPq (PRONEX): 019.203.02712/2009-8
dc.description.sponsorshipIDFEDER Funds: RICET RD12/0018/0003
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fimmu.2017.00227
dc.identifier.citationFrontiers In Immunology. Lausanne, v. 8, p. -, 2017.
dc.identifier.doi10.3389/fimmu.2017.00227
dc.identifier.fileWOS000395547800001.pdf
dc.identifier.issn1664-3224
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54936
dc.identifier.wosWOS:000395547800001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjecthuman visceral leishmaniasisen
dc.subjectnucleoside hydrolaseen
dc.subjectrecombinant domainsen
dc.subjectT cell epitopesen
dc.subjectepitope vaccine designen
dc.subjectLeishmania donovanien
dc.subjectLeishmania infantum chagasien
dc.titleLeishmania donovani nucleoside hydrolase (NH36) Domains induce T-cell cytokine responses in human Visceral leishmaniasisen
dc.typeinfo:eu-repo/semantics/article
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