Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum

Página do item simplificado
dc.contributor.authorBatista, Luis F. S.
dc.contributor.authorUtsunomiya, Yuri T. [UNESP]
dc.contributor.authorSilva, Thais B. F.
dc.contributor.authorDias, Raissa A.
dc.contributor.authorTomokane, Thaise Y.
dc.contributor.authorPacheco, Acacio D. [UNESP]
dc.contributor.authorMatta, Vania L. R. da
dc.contributor.authorSilveira, Fernando T.
dc.contributor.authorMarcondes, Mary [UNESP]
dc.contributor.authorNunes, Caris M. [UNESP]
dc.contributor.authorLaurenti, Marcia D.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionInst Evandro Chagas
dc.date.accessioned2018-11-28T01:36:09Z
dc.date.available2018-11-28T01:36:09Z
dc.date.issued2016-12-01
dc.description.abstractA genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Therefore, we scanned 110,165 single-nucleotide polymorphisms (SNPs), aiming to identify chromosomal regions associated with the leishmanin skin test (LST), lymphocyte proliferation assay (LPA), and cytokine responses to further understand the role played by CMI in the outcome of natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI profiles were identified (LST-/LPA(-), LST+ /LPA(-), LST- /LPA(+), and LST+ /LPA(+)), which were not associated with subclinically infected or diseased dogs. LST+/LPA(+) dogs showed increased interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels and mild parasitism in the lymph nodes, whereas LST-/ LPA(+) dogs, in spite of increased IFN-beta, also showed increased interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) levels and the highest parasite load in lymph nodes. Low T cell proliferation under low parasite load suggested that L. infantum was not able to induce effective CMI in the early stage of infection. Altogether, genetic markers explained 87%, 16%, 15%, 11%, 0%, and 0% of phenotypic variance in TNF-alpha, TGF-beta, LST, IL-10, IFN-gamma, and LPA, respectively. GWAS showed that regions associated with TNF-alpha include the following genes: IL12RB1, JAK3, CCRL2, CCR2, CCR3, and CXCR6, involved in cytokine and chemokine signaling; regions associated with LST, including COMMD5 and SHARPIN, involved in regulation of NF-kappa B signaling; and regions associated with IL-10, including LTBP1 and RASGRP3, involved in T regulatory lymphocytes differentiation. These findings pinpoint chromosomic regions related to the cell-mediated response that potentially affect the clinical complexity and the parasite replication in canine L. infantum infection.en
dc.description.affiliationUniv Sao Paulo, Fac Med Vet & Zootecnia, Dept Patol Vet, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Lab Patol Doencas Infecciosas, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, Dept Clin Cirurgia & Reprod Anim, Fac Med Vet, Sao Paulo, Brazil
dc.description.affiliationInst Evandro Chagas, Dept Parasitol, Ananindeua, Para, Brazil
dc.description.affiliationUniv Estadual Paulista, Dept Saude Anim & Prod, Fac Med Vet, Sao Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet, Sao Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Dept Clin Cirurgia & Reprod Anim, Fac Med Vet, Sao Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Dept Saude Anim & Prod, Fac Med Vet, Sao Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipHospital das Clinicas-Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Brazil
dc.description.sponsorshipIdFAPESP: 2012/50285-9
dc.description.sponsorshipIdFAPESP: 2012/05847-9
dc.description.sponsorshipIdFAPESP: 2014/01095-8
dc.description.sponsorshipIdCNPq: 476479/2012-6
dc.format.extent3629-3637
dc.identifierhttp://dx.doi.org/10.1128/IAI.00486-16
dc.identifier.citationInfection And Immunity. Washington: Amer Soc Microbiology, v. 84, n. 12, p. 3629-3637, 2016.
dc.identifier.doi10.1128/IAI.00486-16
dc.identifier.fileWOS000390128700035.pdf
dc.identifier.issn0019-9567
dc.identifier.lattes1817946671090010
dc.identifier.urihttp://hdl.handle.net/11449/165410
dc.identifier.wosWOS:000390128700035
dc.language.isoeng
dc.publisherAmer Soc Microbiology
dc.relation.ispartofInfection And Immunity
dc.relation.ispartofsjr1,954
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleGenome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantumen
dc.typeArtigo
dcterms.rightsHolderAmer Soc Microbiology
unesp.author.lattes1817946671090010
unesp.author.lattes1892359871207408[10]
unesp.author.orcid0000-0002-5463-3845[10]

Arquivos

Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
WOS000390128700035.pdf
Tamanho:
737.39 KB
Formato:
Adobe Portable Document Format
Descrição:
Baixar

Coleções

Artigos - Clínica, Cirurgia e Reprodução Animal - FMVA