Leishmania donovani nucleoside hydrolase (NH36) Domains induce T-cell cytokine responses in human Visceral leishmaniasis
dc.citation.volume | 8 | |
dc.contributor.author | Barbosa Santos, Micheli Luize | |
dc.contributor.author | Nico, Dirlei | |
dc.contributor.author | de Oliveira, Fabricia Alvisi | |
dc.contributor.author | Barreto, Aline Silva | |
dc.contributor.author | Palatnik-de-Sousa, Iam | |
dc.contributor.author | Carrillo, Eugenia [UNIFESP] | |
dc.contributor.author | Moreno, Javier | |
dc.contributor.author | de Luca, Paula Mello | |
dc.contributor.author | Morrot, Alexandre | |
dc.contributor.author | Rosa, Daniela Santoro [UNIFESP] | |
dc.contributor.author | Palatnik, Marcos | |
dc.contributor.author | Bani-Correa, Cristiane | |
dc.contributor.author | de Almeida, Roque Pacheco | |
dc.contributor.author | Palatnik-de-Sousa, Clarisa Beatriz | |
dc.coverage | Lausanne | |
dc.date.accessioned | 2020-07-17T14:02:40Z | |
dc.date.available | 2020-07-17T14:02:40Z | |
dc.date.issued | 2017 | |
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-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.affiliation | Univ Fed Sergipe HU UFS, Dept Med, Univ Hosp, Mol Biol Lab, Aracaju, Sergipe, Brazil | |
dc.description.affiliation | Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Microbiol Geral, Lab Biol Bioquim Leishmania, Rio De Janeiro, RJ, Brazil | |
dc.description.affiliation | Pontificia Univ Catolica Rio de Janeiro, Lab Biometrol, Programa Posgrad Metrol, Rio De Janeiro, RJ, Brazil | |
dc.description.affiliation | Inst Salud Carlos III, WHO Collaborating Ctr Leishmaniasis, Ctr Nacl Microbiol, Madrid, Comunidad De Ma, Spain | |
dc.description.affiliation | Inst Oswaldo Cruz, Lab Imunoparasitol, Rio De Janeiro, RJ, Brazil | |
dc.description.affiliation | Univ Fed Rio de Janeiro, Inst Microbiologia Paulo de Goes, Dept Imunol, Lab Imunol Integrada, Rio De Janeiro, RJ, Brazil | |
dc.description.affiliation | Univ Sao Paulo, Fac Med, Inst Invest Imunol, Sao Paulo, Brazil | |
dc.description.affiliation | Univ Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Vacinas Expt, Sao Paulo, SP, Brazil | |
dc.description.affiliation | Univ Fed Rio de Janeiro, Fac Med, Lab Imunohematol, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, RJ, Brazil | |
dc.description.affiliation | Univ Fed Sergipe HU UFS, Dept Morfol, Aracaju, Sergipe, Brazil | |
dc.description.affiliationUnifesp | Univ Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Vacinas Expt, Sao Paulo, SP, Brazil | |
dc.description.source | Web of Science | |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) | |
dc.description.sponsorship | Fundacao Carlos Chagas de Amparo a Pesquisa do Estado de Rio de Janeiro (FAPERJ) | |
dc.description.sponsorship | Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior | |
dc.description.sponsorship | CNPQ-Fundacao de Apoio a Pesquisa e a Inovacao Tecnologica do Estado de Sergipe-PRONEX | |
dc.description.sponsorship | FAPITEC CNPq (PRONEX) | |
dc.description.sponsorship | VII PN I+D+I | |
dc.description.sponsorship | FEDER Funds | |
dc.description.sponsorshipID | CNPq: 300639/2003-1 | |
dc.description.sponsorshipID | CNPq: 310977/2014-2 | |
dc.description.sponsorshipID | CNPq: 310797/2015-2 | |
dc.description.sponsorshipID | CNPq: 404400/2012-4 | |
dc.description.sponsorshipID | FAPERJ: E-26-201.583/2014 | |
dc.description.sponsorshipID | FAPERJ: E-26-102957/2011 | |
dc.description.sponsorshipID | FAPERJ: E-26/111.682/2013 | |
dc.description.sponsorshipID | FAPERJ: E-26/102415/2010 | |
dc.description.sponsorshipID | FAPERJ: E-26/201747/2015 | |
dc.description.sponsorshipID | CAPES: 23038.005304/2011-0 | |
dc.description.sponsorshipID | CNPQ-PRONEX: 12/2009 | |
dc.description.sponsorshipID | FAPITEC CNPq (PRONEX): 019.203.02712/2009-8 | |
dc.description.sponsorshipID | FEDER Funds: RICET RD12/0018/0003 | |
dc.format.extent | - | |
dc.identifier | http://dx.doi.org/10.3389/fimmu.2017.00227 | |
dc.identifier.citation | Frontiers In Immunology. Lausanne, v. 8, p. -, 2017. | |
dc.identifier.doi | 10.3389/fimmu.2017.00227 | |
dc.identifier.file | WOS000395547800001.pdf | |
dc.identifier.issn | 1664-3224 | |
dc.identifier.uri | https://repositorio.unifesp.br/handle/11600/54936 | |
dc.identifier.wos | WOS:000395547800001 | |
dc.language.iso | eng | |
dc.publisher | Frontiers Media Sa | |
dc.relation.ispartof | Frontiers In Immunology | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | human visceral leishmaniasis | en |
dc.subject | nucleoside hydrolase | en |
dc.subject | recombinant domains | en |
dc.subject | T cell epitopes | en |
dc.subject | epitope vaccine design | en |
dc.subject | Leishmania donovani | en |
dc.subject | Leishmania infantum chagasi | en |
dc.title | Leishmania donovani nucleoside hydrolase (NH36) Domains induce T-cell cytokine responses in human Visceral leishmaniasis | en |
dc.type | info:eu-repo/semantics/article |
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