Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients

Detalhes bibliográficos
Autor(a) principal: Cunha, Eloisa Helena Medeiros
Data de Publicação: 2023
Outros Autores: Marçal, Pedro Henrique Ferreira, Gama, Rafael Silva, Oliveira, Lorena Bruna Pereira de, Pinheiro, Roberta Olmo, Sarno, Euzenir Nunes, Sousa, Joaquim Pedro Brito de, Souza, Márcio Luís Moreira de, Fairley, Jessica Kathleen, Valente, Thaisa Netto Souza, Rodrigues, Cibele Velloso, Martins Filho, Olindo Assis, Oliveira, Dirce Ribeiro de, Fraga, Lucia Alves de Oliveira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/58981
Resumo: Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
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spelling Cunha, Eloisa Helena MedeirosMarçal, Pedro Henrique FerreiraGama, Rafael SilvaOliveira, Lorena Bruna Pereira dePinheiro, Roberta OlmoSarno, Euzenir NunesSousa, Joaquim Pedro Brito deSouza, Márcio Luís Moreira deFairley, Jessica KathleenValente, Thaisa Netto SouzaRodrigues, Cibele VellosoMartins Filho, Olindo AssisOliveira, Dirce Ribeiro deFraga, Lucia Alves de Oliveira2023-06-09T11:56:47Z2023-06-09T11:56:47Z2023CUNHA, Eloisa Helena Medeiros et al. Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients. Frontiers in Immunology, v. 14, 1130137, p. 1 - 16, Apr. 2023.1664-3224https://www.arca.fiocruz.br/handle/icict/5898110.3389/fimmu.2023.1130137engFrontiers MediaHanseníaseQuimiocinas e citocinasFatores imunológicosFatores genéticosgene TLR4LeprosyChemokines and cytokinesImmunological factorsGenetic factorsTLR4 geneInterplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil /Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz, Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brasil..Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, United States.Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.Fundação Oswaldo Cruz, Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brasil..Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil.Introduction: The aim of the present study was to investigate the association between the single nucleotide polymorphism (SNP) rs1927914 A/G in TLR4 gene and the immunological profile of household contacts (HHC) of leprosy patients. Leprosy classification is usually complex and requires the assessment of several clinical and laboratorial features. Methods: Herein, we have applied distinct models of descriptive analysis to explore qualitative/quantitative changes in chemokine and cytokine production in HHC further categorized according to operational classification [HHC(PB) and HHC(MB)] and according to TLR4SNP. Results and discussion: Our results showed that M. leprae stimuli induced an outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC (PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-g; IL-17) were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine signatures demonstrated that A allele was associated with a prominent soluble mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-g). Data analysis according to TLR4 SNP genotypes further demonstrated that AA and AG were associated with a more prominent secretion of soluble mediators as compared to GG, supporting the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL- 6, TNF and IL-17 displayed distinct profiles in HHC(PB) vs HHC(MB) or AA+AG vs GG genotype. In general, chemokine/cytokine networks analysis showed overall profile of AA+GA-selective (CXCL9–CXCL10) and GG-selective (CXCL10–IL-6) axis regardless of the operational classification. However, mirrored inverted CCL2–IL-10 axis and a (IFN-g–IL-2)-selective axis were identified in HHC(MB). CXCL8 presented outstanding performance to classify AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17 presented elevated accuracy to classify AA+AG from GG genotypes and HHC (PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted that both factors: i) differential exposure to M. leprae and ii) TLR4 rs1927914 genetic background impact the immune response of HHC. Our main results reinforce the relevance of integrated studies of immunological and genetic biomarkers that may have implications to improve the classification and monitoring of HHC in future studies.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/58981/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALEuzenirSarno_etal_IOC_2023.pdfEuzenirSarno_etal_IOC_2023.pdfapplication/pdf18637235https://www.arca.fiocruz.br/bitstream/icict/58981/2/EuzenirSarno_etal_IOC_2023.pdf62093ba212ff5c03c6195ef5266af382MD52icict/589812023-09-04 11:10:24.645oai:www.arca.fiocruz.br:icict/58981Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcwphdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKKDEpIENFREUgZSBUUkFOU0ZFUkUsIHRvdGFsIGUgZ3JhdHVpdGFtZW50ZSwgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaLCBlbQpjYXLDoXRlciBwZXJtYW5lbnRlLCBpcnJldm9nw6F2ZWwgZSBOw4NPIEVYQ0xVU0lWTywgdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08KQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcwpkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBkdXJhbnRlIHRvZG8gbyBwcmF6byBkZSBkdXJhw6fDo28gZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCBlbQpxdWFscXVlciBpZGlvbWEgZSBlbSB0b2RvcyBvcyBwYcOtc2VzOwoKKDIpIEFDRUlUQSBxdWUgYSBjZXNzw6NvIHRvdGFsIG7Do28gZXhjbHVzaXZhLCBwZXJtYW5lbnRlIGUgaXJyZXZvZ8OhdmVsIGRvcyBkaXJlaXRvcyBhdXRvcmFpcwpwYXRyaW1vbmlhaXMgbsOjbyBjb21lcmNpYWlzIGRlIHV0aWxpemHDp8OjbyBkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwKb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciBtZWlvIG91IHZlw61jdWxvLAppbmNsdXNpdmUgZW0gUmVwb3NpdMOzcmlvcyBEaWdpdGFpcywgYmVtIGNvbW8gb3MgZGlyZWl0b3MgZGUgcmVwcm9kdcOnw6NvLCBleGliacOnw6NvLCBleGVjdcOnw6NvLApkZWNsYW1hw6fDo28sIHJlY2l0YcOnw6NvLCBleHBvc2nDp8OjbywgYXJxdWl2YW1lbnRvLCBpbmNsdXPDo28gZW0gYmFuY28gZGUgZGFkb3MsIHByZXNlcnZhw6fDo28sIGRpZnVzw6NvLApkaXN0cmlidWnDp8OjbywgZGl2dWxnYcOnw6NvLCBlbXByw6lzdGltbywgdHJhZHXDp8OjbywgZHVibGFnZW0sIGxlZ2VuZGFnZW0sIGluY2x1c8OjbyBlbSBub3ZhcyBvYnJhcyBvdQpjb2xldMOibmVhcywgcmV1dGlsaXphw6fDo28sIGVkacOnw6NvLCBwcm9kdcOnw6NvIGRlIG1hdGVyaWFsIGRpZMOhdGljbyBlIGN1cnNvcyBvdSBxdWFscXVlciBmb3JtYSBkZQp1dGlsaXphw6fDo28gbsOjbyBjb21lcmNpYWw7CgooMykgUkVDT05IRUNFIHF1ZSBhIGNlc3PDo28gYXF1aSBlc3BlY2lmaWNhZGEgY29uY2VkZSDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPCkNSVVogbyBkaXJlaXRvIGRlIGF1dG9yaXphciBxdWFscXVlciBwZXNzb2Eg4oCTIGbDrXNpY2Egb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdQplc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlcgpmaW5hbGlkYWRlcyBuw6NvIGNvbWVyY2lhaXM7CgooNCkgREVDTEFSQSBxdWUgYSBvYnJhIMOpIGNyaWHDp8OjbyBvcmlnaW5hbCBlIHF1ZSDDqSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGFxdWkgY2VkaWRvcyBlIGF1dG9yaXphZG9zLApyZXNwb25zYWJpbGl6YW5kby1zZSBpbnRlZ3JhbG1lbnRlIHBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwKaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIGluZGVuaXphciB0ZXJjZWlyb3MgcG9yCmRhbm9zLCBiZW0gY29tbyBpbmRlbml6YXIgZSByZXNzYXJjaXIgYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVogZGUKZXZlbnR1YWlzIGRlc3Blc2FzIHF1ZSB2aWVyZW0gYSBzdXBvcnRhciwgZW0gcmF6w6NvIGRlIHF1YWxxdWVyIG9mZW5zYSBhIGRpcmVpdG9zIGF1dG9yYWlzIG91CmRpcmVpdG9zIGRlIHZveiBvdSBpbWFnZW0sIHByaW5jaXBhbG1lbnRlIG5vIHF1ZSBkaXogcmVzcGVpdG8gYSBwbMOhZ2lvIGUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CgooNSkgQUZJUk1BIHF1ZSBjb25oZWNlIGEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTwpPU1dBTERPIENSVVogZSBhcyBkaXJldHJpemVzIHBhcmEgbyBmdW5jaW9uYW1lbnRvIGRvIHJlcG9zaXTDs3JpbyBpbnN0aXR1Y2lvbmFsIEFSQ0EuCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIHJlc2VydmEKZXhjbHVzaXZhbWVudGUgYW8gQVVUT1Igb3MgZGlyZWl0b3MgbW9yYWlzIGUgb3MgdXNvcyBjb21lcmNpYWlzIHNvYnJlIGFzIG9icmFzIGRlIHN1YSBhdXRvcmlhCmUvb3UgdGl0dWxhcmlkYWRlLCBzZW5kbyBvcyB0ZXJjZWlyb3MgdXN1w6FyaW9zIHJlc3BvbnPDoXZlaXMgcGVsYSBhdHJpYnVpw6fDo28gZGUgYXV0b3JpYSBlIG1hbnV0ZW7Dp8OjbwpkYSBpbnRlZ3JpZGFkZSBkYSBPQlJBIGVtIHF1YWxxdWVyIHV0aWxpemHDp8Ojby4KCkEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVoKcmVzcGVpdGEgb3MgY29udHJhdG9zIGUgYWNvcmRvcyBwcmVleGlzdGVudGVzIGRvcyBBdXRvcmVzIGNvbSB0ZXJjZWlyb3MsIGNhYmVuZG8gYW9zIEF1dG9yZXMKaW5mb3JtYXIgw6AgSW5zdGl0dWnDp8OjbyBhcyBjb25kacOnw7VlcyBlIG91dHJhcyByZXN0cmnDp8O1ZXMgaW1wb3N0YXMgcG9yIGVzdGVzIGluc3RydW1lbnRvcy4KRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:10:24Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
title Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
spellingShingle Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
Cunha, Eloisa Helena Medeiros
Hanseníase
Quimiocinas e citocinas
Fatores imunológicos
Fatores genéticos
gene TLR4
Leprosy
Chemokines and cytokines
Immunological factors
Genetic factors
TLR4 gene
title_short Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
title_full Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
title_fullStr Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
title_full_unstemmed Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
title_sort Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
author Cunha, Eloisa Helena Medeiros
author_facet Cunha, Eloisa Helena Medeiros
Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Sousa, Joaquim Pedro Brito de
Souza, Márcio Luís Moreira de
Fairley, Jessica Kathleen
Valente, Thaisa Netto Souza
Rodrigues, Cibele Velloso
Martins Filho, Olindo Assis
Oliveira, Dirce Ribeiro de
Fraga, Lucia Alves de Oliveira
author_role author
author2 Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Sousa, Joaquim Pedro Brito de
Souza, Márcio Luís Moreira de
Fairley, Jessica Kathleen
Valente, Thaisa Netto Souza
Rodrigues, Cibele Velloso
Martins Filho, Olindo Assis
Oliveira, Dirce Ribeiro de
Fraga, Lucia Alves de Oliveira
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Cunha, Eloisa Helena Medeiros
Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Sousa, Joaquim Pedro Brito de
Souza, Márcio Luís Moreira de
Fairley, Jessica Kathleen
Valente, Thaisa Netto Souza
Rodrigues, Cibele Velloso
Martins Filho, Olindo Assis
Oliveira, Dirce Ribeiro de
Fraga, Lucia Alves de Oliveira
dc.subject.other.en_US.fl_str_mv Hanseníase
Quimiocinas e citocinas
Fatores imunológicos
Fatores genéticos
gene TLR4
topic Hanseníase
Quimiocinas e citocinas
Fatores imunológicos
Fatores genéticos
gene TLR4
Leprosy
Chemokines and cytokines
Immunological factors
Genetic factors
TLR4 gene
dc.subject.en.en_US.fl_str_mv Leprosy
Chemokines and cytokines
Immunological factors
Genetic factors
TLR4 gene
description Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brasil / Universidade Vale do Rio Doce – Univale, Departamento de Ciências da Saúde. Governador Valadares, MG, Brasil.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-06-09T11:56:47Z
dc.date.available.fl_str_mv 2023-06-09T11:56:47Z
dc.date.issued.fl_str_mv 2023
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.citation.fl_str_mv CUNHA, Eloisa Helena Medeiros et al. Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients. Frontiers in Immunology, v. 14, 1130137, p. 1 - 16, Apr. 2023.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/58981
dc.identifier.issn.en_US.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2023.1130137
identifier_str_mv CUNHA, Eloisa Helena Medeiros et al. Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients. Frontiers in Immunology, v. 14, 1130137, p. 1 - 16, Apr. 2023.
1664-3224
10.3389/fimmu.2023.1130137
url https://www.arca.fiocruz.br/handle/icict/58981
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/58981/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/58981/2/EuzenirSarno_etal_IOC_2023.pdf
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repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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