Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1128/IAI.00486-16 http://hdl.handle.net/11449/165410 |
Resumo: | 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. |
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Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantumA 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Hospital das Clinicas-Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), BrazilUniv Sao Paulo, Fac Med Vet & Zootecnia, Dept Patol Vet, Sao Paulo, BrazilUniv Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet, Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Lab Patol Doencas Infecciosas, Sao Paulo, BrazilUniv Estadual Paulista, Dept Clin Cirurgia & Reprod Anim, Fac Med Vet, Sao Paulo, BrazilInst Evandro Chagas, Dept Parasitol, Ananindeua, Para, BrazilUniv Estadual Paulista, Dept Saude Anim & Prod, Fac Med Vet, Sao Paulo, BrazilUniv Estadual Paulista, Dept Med Vet Prevent & Reprod Anim, Fac Ciencias Agr & Vet, Sao Paulo, BrazilUniv Estadual Paulista, Dept Clin Cirurgia & Reprod Anim, Fac Med Vet, Sao Paulo, BrazilUniv Estadual Paulista, Dept Saude Anim & Prod, Fac Med Vet, Sao Paulo, BrazilFAPESP: 2012/50285-9FAPESP: 2012/05847-9FAPESP: 2014/01095-8CNPq: 476479/2012-6Amer Soc MicrobiologyUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Inst Evandro ChagasBatista, Luis F. S.Utsunomiya, Yuri T. [UNESP]Silva, Thais B. F.Dias, Raissa A.Tomokane, Thaise Y.Pacheco, Acacio D. [UNESP]Matta, Vania L. R. daSilveira, Fernando T.Marcondes, Mary [UNESP]Nunes, Caris M. [UNESP]Laurenti, Marcia D.2018-11-28T01:36:09Z2018-11-28T01:36:09Z2016-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article3629-3637application/pdfhttp://dx.doi.org/10.1128/IAI.00486-16Infection And Immunity. Washington: Amer Soc Microbiology, v. 84, n. 12, p. 3629-3637, 2016.0019-9567http://hdl.handle.net/11449/16541010.1128/IAI.00486-16WOS:000390128700035WOS000390128700035.pdf1817946671090010Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInfection And Immunity1,954info:eu-repo/semantics/openAccess2024-01-19T06:31:42Zoai:repositorio.unesp.br:11449/165410Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-19T06:31:42Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
title |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
spellingShingle |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum Batista, Luis F. S. |
title_short |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
title_full |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
title_fullStr |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
title_full_unstemmed |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
title_sort |
Genome-Wide Association Study of Cell-Mediated Response in Dogs Naturally Infected by Leishmania infantum |
author |
Batista, Luis F. S. |
author_facet |
Batista, Luis F. S. Utsunomiya, Yuri T. [UNESP] Silva, Thais B. F. Dias, Raissa A. Tomokane, Thaise Y. Pacheco, Acacio D. [UNESP] Matta, Vania L. R. da Silveira, Fernando T. Marcondes, Mary [UNESP] Nunes, Caris M. [UNESP] Laurenti, Marcia D. |
author_role |
author |
author2 |
Utsunomiya, Yuri T. [UNESP] Silva, Thais B. F. Dias, Raissa A. Tomokane, Thaise Y. Pacheco, Acacio D. [UNESP] Matta, Vania L. R. da Silveira, Fernando T. Marcondes, Mary [UNESP] Nunes, Caris M. [UNESP] Laurenti, Marcia D. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Inst Evandro Chagas |
dc.contributor.author.fl_str_mv |
Batista, Luis F. S. Utsunomiya, Yuri T. [UNESP] Silva, Thais B. F. Dias, Raissa A. Tomokane, Thaise Y. Pacheco, Acacio D. [UNESP] Matta, Vania L. R. da Silveira, Fernando T. Marcondes, Mary [UNESP] Nunes, Caris M. [UNESP] Laurenti, Marcia D. |
description |
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. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12-01 2018-11-28T01:36:09Z 2018-11-28T01:36:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1128/IAI.00486-16 Infection And Immunity. Washington: Amer Soc Microbiology, v. 84, n. 12, p. 3629-3637, 2016. 0019-9567 http://hdl.handle.net/11449/165410 10.1128/IAI.00486-16 WOS:000390128700035 WOS000390128700035.pdf 1817946671090010 |
url |
http://dx.doi.org/10.1128/IAI.00486-16 http://hdl.handle.net/11449/165410 |
identifier_str_mv |
Infection And Immunity. Washington: Amer Soc Microbiology, v. 84, n. 12, p. 3629-3637, 2016. 0019-9567 10.1128/IAI.00486-16 WOS:000390128700035 WOS000390128700035.pdf 1817946671090010 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Infection And Immunity 1,954 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
3629-3637 application/pdf |
dc.publisher.none.fl_str_mv |
Amer Soc Microbiology |
publisher.none.fl_str_mv |
Amer Soc Microbiology |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965665774272512 |