Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum
dc.contributor.author | Batista, Luis F. S. | |
dc.contributor.author | Utsunomiya, Yuri T. [UNESP] | |
dc.contributor.author | Silva, Thais B. F. | |
dc.contributor.author | Dias, Raissa A. | |
dc.contributor.author | Tomokane, Thaise Y. | |
dc.contributor.author | Pacheco, Acacio D. [UNESP] | |
dc.contributor.author | Matta, Vania L. R. da | |
dc.contributor.author | Silveira, Fernando T. | |
dc.contributor.author | Marcondes, Mary [UNESP] | |
dc.contributor.author | Nunes, Caris M. [UNESP] | |
dc.contributor.author | Laurenti, Marcia D. | |
dc.contributor.institution | Universidade de São Paulo (USP) | |
dc.contributor.institution | Universidade Estadual Paulista (Unesp) | |
dc.contributor.institution | Inst Evandro Chagas | |
dc.date.accessioned | 2018-11-28T01:36:09Z | |
dc.date.available | 2018-11-28T01:36:09Z | |
dc.date.issued | 2016-12-01 | |
dc.description.abstract | A 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.affiliation | Univ Sao Paulo, Fac Med Vet & Zootecnia, Dept Patol Vet, Sao Paulo, Brazil | |
dc.description.affiliation | Univ Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet, Sao Paulo, Brazil | |
dc.description.affiliation | Univ Sao Paulo, Fac Med, Lab Patol Doencas Infecciosas, Sao Paulo, Brazil | |
dc.description.affiliation | Univ Estadual Paulista, Dept Clin Cirurgia & Reprod Anim, Fac Med Vet, Sao Paulo, Brazil | |
dc.description.affiliation | Inst Evandro Chagas, Dept Parasitol, Ananindeua, Para, Brazil | |
dc.description.affiliation | Univ Estadual Paulista, Dept Saude Anim & Prod, Fac Med Vet, Sao Paulo, Brazil | |
dc.description.affiliationUnesp | Univ Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet, Sao Paulo, Brazil | |
dc.description.affiliationUnesp | Univ Estadual Paulista, Dept Clin Cirurgia & Reprod Anim, Fac Med Vet, Sao Paulo, Brazil | |
dc.description.affiliationUnesp | Univ Estadual Paulista, Dept Saude Anim & Prod, Fac Med Vet, Sao Paulo, Brazil | |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | |
dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | |
dc.description.sponsorship | Hospital das Clinicas-Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Brazil | |
dc.description.sponsorshipId | FAPESP: 2012/50285-9 | |
dc.description.sponsorshipId | FAPESP: 2012/05847-9 | |
dc.description.sponsorshipId | FAPESP: 2014/01095-8 | |
dc.description.sponsorshipId | CNPq: 476479/2012-6 | |
dc.format.extent | 3629-3637 | |
dc.identifier | http://dx.doi.org/10.1128/IAI.00486-16 | |
dc.identifier.citation | Infection And Immunity. Washington: Amer Soc Microbiology, v. 84, n. 12, p. 3629-3637, 2016. | |
dc.identifier.doi | 10.1128/IAI.00486-16 | |
dc.identifier.file | WOS000390128700035.pdf | |
dc.identifier.issn | 0019-9567 | |
dc.identifier.lattes | 1817946671090010 | |
dc.identifier.uri | http://hdl.handle.net/11449/165410 | |
dc.identifier.wos | WOS:000390128700035 | |
dc.language.iso | eng | |
dc.publisher | Amer Soc Microbiology | |
dc.relation.ispartof | Infection And Immunity | |
dc.relation.ispartofsjr | 1,954 | |
dc.rights.accessRights | Acesso aberto | |
dc.source | Web of Science | |
dc.title | Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum | en |
dc.type | Artigo | |
dcterms.rightsHolder | Amer Soc Microbiology | |
unesp.author.lattes | 1817946671090010 | |
unesp.author.lattes | 1892359871207408[10] | |
unesp.author.orcid | 0000-0002-5463-3845[10] |
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